Thrombosis at Unusual Sites: Focus on Myeloproliferative Neoplasms and Paroxysmal Nocturnal Hemoglobinuria

 

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Abstract

Patients with thrombosis at an unusual site will need to be explored for rare causes of thrombosis. Two of these rare causes include myeloproliferative neoplasms (MPNs) and paroxysmal nocturnal hemoglobinuria (PNH). It is important not to overlook these causes, since they require specific management, in addition to antithrombotic treatment (anticoagulants, antiplatelet agents). Unusual sites of venous thrombosis include upper extremity veins, splanchnic veins, cerebral veins, and retinal veins, and unusual sites of arterial thrombosis include renal, adrenal, splenic and mesenteric arteries, and intracardiac and aortal locations. Suspicion for MPN and PNH should be raised if there are concomitant abnormalities, such as elevated or decreased blood cell counts or splenomegaly. Diagnosis of MPN and PNH should include JAK2V617F mutational screening as well as flow cytometric assessment of GPI-anchored proteins in the peripheral blood, respectively. Specific treatments for MPN may include phlebotomy or cytoreductive drugs such as hydroxyurea, anagrelide, pegylated interferon-alpha, or Janus kinase inhibitors. Drugs used for PNH treatment include terminal complement inhibitors, such as eculizumab and ravulizumab, as well as proximally acting inhibitors such as pegcetacoplan or iptacopan. Patients with MPN and PNH are at high risk for thrombosis during their entire lifetime and should thus be followed by specialists experienced in the care of these diseases.

Zusammenfassung

Patienten mit einer Thrombose an einer ungewöhnlichen Lokalisation müssen auf seltene Thrombose-Ursachen hin untersucht werden. Zwei dieser seltenen Ursachen sind Myeloproliferative Neoplasien (MPN) und die Paroxysmale Nächtliche Hämoglobinurie (PNH). Es ist wichtig, diese Ursachen nicht zu übersehen, da Patienten mit diesen Erkrankungen neben einer antithrombotischen Behandlung (Antikoagulanzien, Thrombozytenaggregationshemmer) eine spezifische Behandlung benötigen. Ungewöhnliche Lokalisationen für Venenthrombosen sind Venen der oberen Extremitäten, Splanchnikusvenen, Hirnvenen und Netzhautvenen, während ungewöhnliche Stellen für arterielle Thrombosen Nieren-, Nebennieren-, Milz- und Mesenterialarterien sowie intrakardiale und aortale Lokalisationen darstellen. Der Verdacht auf das Vorliegen einer MPN oder einer PNH sollte insbesondere dann geschöpft werden, wenn gleichzeitig weitere klinische Auffälligkeiten wie eine erhöhte oder verringerte Blutzellanzahl oder Splenomegalie vorliegen. Die Diagnose von MPN und PNH sollte ein JAK2V617F-Mutationsscreening bzw. eine durchflusszytometrische Bewertung von GPI-verankerten Proteinen im peripheren Blut umfassen. Zu den spezifischen Behandlungen für MPN können Aderlässe oder zytoreduktive Medikamente wie Hydroxycarbamid, Anagrelid, pegyliertes Interferon-alpha oder JAK-Inhibitoren gehören. Zu den zur Behandlung von PNH verwendeten Medikamenten gehören terminale Komplementinhibitoren wie Eculizumab und Ravulizumab sowie proximal wirkende Inhibitoren wie Pegcetacoplan oder Iptacopan. Patienten mit MPN und PNH haben während ihres gesamten Lebens ein hohes Thromboserisiko und sollten daher von Spezialisten betreut werden, die über Erfahrung in der Behandlung dieser Krankheiten verfügen.

Publication History

Received: 12 September 2024

Accepted: 19 November 2024

Article published online:
03 February 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

• References

• 1 Zakai NA, McClure LA, Judd SE. et al. Racial and regional differences in venous thromboembolism in the United States in 3 cohorts. Circulation 2014; 129 (14) 1502-1509
  CrossrefPubMedSearch in Google Scholar
• 2 Isma N, Svensson PJ, Gottsäter A, Lindblad B. Prospective analysis of risk factors and distribution of venous thromboembolism in the population-based Malmö Thrombophilia Study (MATS). Thromb Res 2009; 124 (06) 663-666
  CrossrefPubMedSearch in Google Scholar
• 3 Isma N, Svensson PJ, Gottsäter A, Lindblad B. Upper extremity deep venous thrombosis in the population-based Malmö thrombophilia study (MATS). Epidemiology, risk factors, recurrence risk, and mortality. Thromb Res 2010; 125 (06) e335-e338
  CrossrefPubMedSearch in Google Scholar
• 4 Creager MA, Kaufman JA, Conte MS. Clinical practice. Acute limb ischemia. N Engl J Med 2012; 366 (23) 2198-2206
  CrossrefPubMedSearch in Google Scholar
• 5 Mozaffarian D, Benjamin EJ, Go AS. et al; Writing Group Members, American Heart Association Statistics Committee, Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 update: a report from the American Heart Association. Circulation 2016; 133 (04) e38-e360
  PubMedSearch in Google Scholar
• 6 White H, Boden-Albala B, Wang C. et al. Ischemic stroke subtype incidence among whites, blacks, and Hispanics: the Northern Manhattan Study. Circulation 2005; 111 (10) 1327-1331
  CrossrefPubMedSearch in Google Scholar
• 7 Ageno W. Treatment of atypical clots. Hamostaseologie 2022; 42 (01) 10-18
  Thieme ConnectPubMedSearch in Google Scholar
• 8 Koschmieder S, How I. How I manage thrombotic/thromboembolic complications in myeloproliferative neoplasms. Hamostaseologie 2020; 40 (01) 47-53
  Thieme ConnectPubMedSearch in Google Scholar
• 9 Kaifie A, Kirschner M, Wolf D. et al; Study Alliance Leukemia (SAL). Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 2016; 9: 18
  CrossrefPubMedSearch in Google Scholar
• 10 Kreher S, Ochsenreither S, Trappe RU. et al; Haemostasis Working Party of the German Society of Hematology and Oncology, Austrian Society of Hematology and Oncology, Society of Thrombosis and Haemostasis Research. Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.). Ann Hematol 2014; 93 (12) 1953-1963
  CrossrefPubMedSearch in Google Scholar
• 11 Barbui T, Tefferi A, Vannucchi AM. et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 2018; 32 (05) 1057-1069
  CrossrefPubMedSearch in Google Scholar
• 12 Panse J. Paroxysmal nocturnal hemoglobinuria: where we stand. Am J Hematol 2023; 98 (Suppl. 04) S20-S32
  PubMedSearch in Google Scholar
• 13 Oliver M, Patriquin CJ. Paroxysmal nocturnal hemoglobinuria: current management, unmet needs, and recommendations. J Blood Med 2023; 14: 613-628
  CrossrefPubMedSearch in Google Scholar
• 14 Sicre de Fontbrune F, Burmester P, Piggin M. et al. The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors: clinical outcomes and medical encounters from the patient perspective. Hematology 2022; 27 (01) 1140-1151
  CrossrefPubMedSearch in Google Scholar
• 15 Rungjirajittranon T, Owattanapanich W, Ungprasert P, Siritanaratkul N, Ruchutrakool T. A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms. BMC Cancer 2019; 19 (01) 184
  CrossrefPubMedSearch in Google Scholar
• 16 Görtzen J, Hunka LM, Vonnahme M. et al. γ-Glutamyl transferase is an independent biomarker of splanchnic thrombosis in patients with myeloproliferative neoplasm. Medicine (Baltimore) 2016; 95 (20) e3355
  CrossrefPubMedSearch in Google Scholar
• 17 Khaddam D, McRae HL, Schwarz N. et al. High prevalence of F2 20210G > A in splanchnic vein thrombosis and cerebral venous sinus thrombosis: a retrospective cohort study of patients with thrombosis in atypical sites. Hamostaseologie 2024; (e-pub ahead of print)
  Thieme ConnectPubMedSearch in Google Scholar
• 18 De Stefano V, Fiorini A, Rossi E. et al. Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 2007; 5 (04) 708-714
  CrossrefPubMedSearch in Google Scholar
• 19 Smalberg JH, Arends LR, Valla DC, Kiladjian JJ, Janssen HL, Leebeek FW. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood 2012; 120 (25) 4921-4928
  CrossrefPubMedSearch in Google Scholar
• 20 O'Donnell M, Shatzel JJ, Olson SR. et al. Arterial thrombosis in unusual sites: a practical review. Eur J Haematol 2018; 101 (06) 728-736
  CrossrefPubMedSearch in Google Scholar
• 21 De Stefano V, Ruggeri M, Cervantes F. et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia 2016; 30 (10) 2032-2038
  CrossrefPubMedSearch in Google Scholar
• 22 De Stefano V, Vannucchi AM, Ruggeri M. et al. Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. Blood Cancer J 2016; 6 (11) e493
  CrossrefPubMedSearch in Google Scholar
• 23 De Stefano V, Finazzi G, Barbui T. Antithrombotic therapy for venous thromboembolism in myeloproliferative neoplasms. Blood Cancer J 2018; 8 (07) 65
  CrossrefPubMedSearch in Google Scholar
• 24 Barbui T, Finazzi G, Carobbio A. et al. Development and validation of an international prognostic score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 2012; 120 (26) 5128-5133 , quiz 5252
  CrossrefPubMedSearch in Google Scholar
• 25 Cortelazzo S, Finazzi G, Ruggeri M. et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995; 332 (17) 1132-1136
  CrossrefPubMedSearch in Google Scholar
• 26 Landolfi R, Marchioli R, Kutti J. et al; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004; 350 (02) 114-124
  CrossrefPubMedSearch in Google Scholar
• 27 Barbui T, Vannucchi AM, Finazzi G. et al. A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: a propensity-matched study. Am J Hematol 2017; 92 (11) 1131-1136
  CrossrefPubMedSearch in Google Scholar
• 28 Luzzatto L, Gianfaldoni G, Notaro R. Management of paroxysmal nocturnal haemoglobinuria: a personal view. Br J Haematol 2011; 153 (06) 709-720
  CrossrefPubMedSearch in Google Scholar
• 29 Gurnari C, Awada H, Pagliuca S. et al. Paroxysmal nocturnal hemoglobinuria-related thrombosis in the era of novel therapies: a 2043-patient-year analysis. Blood 2024; 144 (02) 145-155
  CrossrefPubMedSearch in Google Scholar
• 30 McKeage K. Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. Drugs 2011; 71 (17) 2327-2345
  CrossrefPubMedSearch in Google Scholar
• 31 Hillmen P, Muus P, Dührsen U. et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007; 110 (12) 4123-4128
  CrossrefPubMedSearch in Google Scholar
• 32 Schmidt CQ, Höchsmann B, Schrezenmeier H. The complement model disease paroxysmal nocturnal hemoglobinuria. Eur J Immunol 2024; 54 (11) e2350817
  CrossrefPubMedSearch in Google Scholar
• 33 Brodsky RA. New insights into paroxysmal nocturnal hemoglobinuria. Hematology (Am Soc Hematol Educ Program) 2006; 24–8: 24-28 , 516
  CrossrefPubMedSearch in Google Scholar
• 34 Van Bijnen ST, Van Heerde WL, Muus P. Mechanisms and clinical implications of thrombosis in paroxysmal nocturnal hemoglobinuria. J Thromb Haemost 2012; 10 (01) 1-10
  CrossrefPubMedSearch in Google Scholar
• 35 Schmidt CQ, Schrezenmeier H, Kavanagh D. Complement and the prothrombotic state. Blood 2022; 139 (13) 1954-1972
  CrossrefPubMedSearch in Google Scholar
• 36 Weitz IC. Complement the hemostatic system: an intimate relationship. Thromb Res 2014; 133 (Suppl. 02) S117-S121
  CrossrefPubMedSearch in Google Scholar
• 37 Cappellini MD. Coagulation in the pathophysiology of hemolytic anemias. Hematology (Am Soc Hematol Educ Program) 2007; 74–8: 74-78
  CrossrefPubMedSearch in Google Scholar
• 38 Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2013; 121 (25) 4985-4996 , quiz 5105
  CrossrefPubMedSearch in Google Scholar
• 39 Griffin M, Munir T. Management of thrombosis in paroxysmal nocturnal hemoglobinuria: a clinician's guide. Ther Adv Hematol 2017; 8 (03) 119-126
  CrossrefPubMedSearch in Google Scholar
• 40 Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995; 333 (19) 1253-1258
  CrossrefPubMedSearch in Google Scholar
• 41 Socié G, Mary JY, de Gramont A. et al; French Society of Haematology. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet 1996; 348 (9027) 573-577
  CrossrefPubMedSearch in Google Scholar
• 42 de Latour RP, Mary JY, Salanoubat C. et al; French Society of Hematology, French Association of Young Hematologists. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood 2008; 112 (08) 3099-3106
  CrossrefPubMedSearch in Google Scholar
• 43 Nishimura JI, Kanakura Y, Ware RE. et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore) 2004; 83 (03) 193-207
  CrossrefPubMedSearch in Google Scholar
• 44 Yu F, Du Y, Han B. A comparative analysis of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria between Asia and Europe/America. Int J Hematol 2016; 103 (06) 649-654
  CrossrefPubMedSearch in Google Scholar
• 45 Jang JH, Kim JS, Yoon SS. et al. Predictive factors of mortality in population of patients with paroxysmal nocturnal hemoglobinuria (PNH): results from a Korean PNH registry. J Korean Med Sci 2016; 31 (02) 214-221
  CrossrefPubMedSearch in Google Scholar
• 46 Nissen-Meyer LS, Tjønnfjord GE, Golebiowska E, Kjeldsen-Kragh J, Akkök CA. Paroxysmal nocturnal haemoglobinuria at Oslo University Hospital 2000-2010. Tidsskr Nor Laegeforen 2015; 135 (11) 1039-1043
  PubMedSearch in Google Scholar
• 47 Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 2005; 293 (13) 1653-1662
  CrossrefPubMedSearch in Google Scholar
• 48 Keragala CB, Draxler DF, McQuilten ZK, Medcalf RL. Haemostasis and innate immunity - a complementary relationship: a review of the intricate relationship between coagulation and complement pathways. Br J Haematol 2018; 180 (06) 782-798
  CrossrefPubMedSearch in Google Scholar
• 49 Ninan GA, Miraclin T A, Karumathil S. et al. Interventions in cerebrovascular emergencies among patients with paroxysmal nocturnal haemoglobinuria - a word of caution. J Stroke Cerebrovasc Dis 2023; 32 (11) 107305
  CrossrefPubMedSearch in Google Scholar
• 50 Menosi Gualandro SF, Salvino MA, Bassolli de Oliveira Alves L, Jehá T. Characteristics of paroxysmal nocturnal hemoglobinuria patients in Brazil: a retrospective administrative claims database analysis of PNH patients in Brazilian public healthcare system. PLoS One 2023; 18 (07) e0288708
  CrossrefPubMedSearch in Google Scholar
• 51 Zhao H, Shattil S. Cutaneous thrombosis in PNH. Blood 2013; 122 (19) 3249
  CrossrefPubMedSearch in Google Scholar
• 52 Biggart R, Davies C, Joshi N. A review of systemic hematological manifestations and stent thrombosis. Cardiol Rev 2023; Feb 24: e000535 . Epub ahead of print. PMID: 36825903
  CrossrefPubMedSearch in Google Scholar
• 53 Ziakas PD, Poulou LS, Rokas GI, Bartzoudis D, Voulgarelis M. Thrombosis in paroxysmal nocturnal hemoglobinuria: sites, risks, outcome. An overview. J Thromb Haemost 2007; 5 (03) 642-645
  CrossrefPubMedSearch in Google Scholar
• 54 Beckmann L, Faizy TD, Flottmann F. et al. Multisite thrombosis in a patient with paroxysmal nocturnal hemoglobinuria. Hamostaseologie 2024; Feb 9. . Epub ahead of print. PMID: 38335997
  Thieme ConnectPubMedSearch in Google Scholar
• 55 Xiao M, Di Y, An Y, Cui Y. Acute necrotizing pancreatitis complicated with paroxysmal nocturnal haemoglobinuria: a case report. Clin Exp Gastroenterol 2024; 17: 141-145
  CrossrefPubMedSearch in Google Scholar
• 56 Porel R, Kumar A, Ajit S, Ojha VS, Biswas R. Classic paroxysmal nocturnal haemoglobinuria presenting with intestinal malabsorption syndrome, acute abdomen and acute kidney injury. BMJ Case Rep 2024; 17 (03) e258785
  CrossrefPubMedSearch in Google Scholar
• 57 Du R, Zheng L, Liu P. et al. Case report: paroxysmal nocturnal hemoglobinuria presenting with hemorrhagic esophageal varices. Front Med (Lausanne) 2023; 10: 1276030
  CrossrefPubMedSearch in Google Scholar
• 58 Chatzileontiadou S, Hatjiharissi E, Angelopoulou M. et al. Thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): real world data of a Greek nationwide multicenter retrospective study. Front Oncol 2023; 13: 1128994
  CrossrefPubMedSearch in Google Scholar
• 59 Lazo-Langner A, Kovacs MJ, Hedley B. et al. Screening of patients with idiopathic venous thromboembolism for paroxysmal nocturnal hemoglobinuria clones. Thromb Res 2015; 135 (06) 1107-1109
  CrossrefPubMedSearch in Google Scholar
• 60 Rovó A, Gavillet M, Drexler B. et al. Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones. Front Med (Lausanne) 2023; 10: 1200431
  CrossrefPubMedSearch in Google Scholar
• 61 de Franchis R, Baveno VIF. Baveno VI Faculty. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63 (03) 743-752
  CrossrefPubMedSearch in Google Scholar
• 62 Hoekstra J, Leebeek FW, Plessier A. et al; European Network for Vascular Disorders of the Liver. Paroxysmal nocturnal hemoglobinuria in Budd-Chiari syndrome: findings from a cohort study. J Hepatol 2009; 51 (04) 696-706
  CrossrefPubMedSearch in Google Scholar
• 63 Alukal JJ, Zhang T, Thuluvath PJ. A nationwide analysis of Budd-Chiari syndrome in the United States. J Clin Exp Hepatol 2021; 11 (02) 181-187
  CrossrefPubMedSearch in Google Scholar
• 64 Ozdemir ZN, Ilhan O, Ozet G. et al. Study for the diagnostic screening of paroxysmal nocturnal hemoglobinuria in older patients with unexplained anemia and/or cytopenia. Clin Lab 2020; Sep 1; 66 (09) . PMID: 32902222
  CrossrefPubMedSearch in Google Scholar
• 65 Whitby L, White J, Fletcher M, Whitby A, Milkins C, Barnett D. Paroxysmal nocturnal haemoglobinuria testing in blood transfusion laboratories: do they go with the flow?. Transfus Med 2018; 28 (06) 451-456
  CrossrefPubMedSearch in Google Scholar
• 66 Sutherland DR, Kuek N, Azcona-Olivera J. et al. Use of a FLAER-based WBC assay in the primary screening of PNH clones. Am J Clin Pathol 2009; 132 (04) 564-572
  CrossrefPubMedSearch in Google Scholar
• 67 Meppiel E, Crassard I, Latour RP. et al. Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria: a series of 15 cases and review of the literature. Medicine (Baltimore) 2015; 94 (01) e362
  CrossrefPubMedSearch in Google Scholar
• 68 Alashkar F, Saner FH, Vance C. et al. Pregnancy in classical paroxysmal nocturnal hemoglobinuria and aplastic anemia-paroxysmal nocturnal hemoglobinuria: a high-risk constellation. Front Med (Lausanne) 2020; Sep 24; 7: 543372 . PMID: 33102497; PMCID: PMC7546795.
  CrossrefPubMedSearch in Google Scholar
• 69 Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood 2021; 137 (10) 1304-1309
  CrossrefPubMedSearch in Google Scholar
• 70 Szer J. Thrombosis in PNH: largely gone, but not forgotten. Blood 2024; 144 (02) 125-126
  CrossrefPubMedSearch in Google Scholar
• 71 Loschi M, Porcher R, Barraco F. et al. Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study. Am J Hematol 2016; 91 (04) 366-370
  CrossrefPubMedSearch in Google Scholar
• 72 Höchsmann B, de Fontbrune FS, Lee JW. et al. Effect of eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria with or without high disease activity: real-world findings from the International Paroxysmal Nocturnal Hemoglobinuria Registry. Eur J Haematol 2022; 109 (03) 197-204
  CrossrefPubMedSearch in Google Scholar
• 73 Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood 2003; 102 (10) 3587-3591
  CrossrefPubMedSearch in Google Scholar
• 74 Dingli D, Maciejewski JP, Larratt L. et al. Relationship of paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size to disease burden and risk of major vascular events in untreated patients: results from the International PNH Registry. Ann Hematol 2023; 102 (07) 1637-1644
  CrossrefPubMedSearch in Google Scholar
• 75 Schrezenmeier H, Muus P, Socié G. et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica 2014; 99 (05) 922-929
  CrossrefPubMedSearch in Google Scholar
• 76 Richards SJ, Dickinson AJ, Cullen MJ. et al. Presentation clinical, haematological and immunophenotypic features of 1081 patients with GPI-deficient (paroxysmal nocturnal haemoglobinuria) cells detected by flow cytometry. Br J Haematol 2020; 189 (05) 954-966
  CrossrefPubMedSearch in Google Scholar
• 77 Kulasekararaj AG, Lazana I. Paroxysmal nocturnal hemoglobinuria: where are we going. Am J Hematol 2023; 98 (Suppl. 04) S33-S43
  PubMedSearch in Google Scholar
• 78 Gavriilaki E, de Latour RP, Risitano AM. Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond. Blood 2022; 139 (25) 3571-3582
  CrossrefPubMedSearch in Google Scholar
• 79 Kelly RJ, Nishimori H, Horneff R. et al. Thrombosis and meningococcal infection rates in pegcetacoplan-treated patients with paroxysmal nocturnal hemoglobinuria in the clinical trial and postmarketing settings. Res Pract Thromb Haemost 2024; 8 (04) 102416
  CrossrefPubMedSearch in Google Scholar
• 80 Gerber GF, DeZern AE, Chaturvedi S, Brodsky RA. A 15-year, single institution experience of anticoagulation management in paroxysmal nocturnal hemoglobinuria patients on terminal complement inhibition with history of thromboembolism. Am J Hematol 2022; 97 (02) E59-E62
  CrossrefPubMedSearch in Google Scholar
• 81 Emadi A, Brodsky RA. Successful discontinuation of anticoagulation following eculizumab administration in paroxysmal nocturnal hemoglobinuria. Am J Hematol 2009; 84 (10) 699-701
  CrossrefPubMedSearch in Google Scholar
• 82 Skeith L. Anticoagulating patients with high-risk acquired thrombophilias. Blood 2018; 132 (21) 2219-2229
  CrossrefPubMedSearch in Google Scholar
• 83 Risitano AM, Marotta S, Ricci P. et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol 2019; 10: 1157
  CrossrefPubMedSearch in Google Scholar
• 84 Griffin M, Kelly RJ, Panse J. et al. Management of acute breakthrough hemolysis with intensive pegcetacoplan dosing in patients with PNH. Blood Adv 2024; 8 (07) 1776-1786
  CrossrefPubMedSearch in Google Scholar
• 85 Griffin M, Kelly R, Brindel I. et al. Real-world experience of pegcetacoplan in paroxysmal nocturnal hemoglobinuria. Am J Hematol 2024; 99 (05) 816-823
  CrossrefPubMedSearch in Google Scholar
• 86 Dingli D, De Castro III C, Koprivnikar J. et al. Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria. Hematology 2024; 29 (01) 2329030
  CrossrefPubMedSearch in Google Scholar
• 87 Iino T, Yokoo M, Okamoto S, Kondo S. Aplastic anemia with thrombosis following the administration of immunosuppressant and thrombopoietin receptor agonist (TPO-RA). Cureus 2024; 16 (05) e61135
  PubMedSearch in Google Scholar
• 88 Hill A, de Latour RP, Kulasekararaj AG. et al. Concomitant immunosuppressive therapy and eculizumab use in patients with paroxysmal nocturnal hemoglobinuria: an international PNH registry analysis. Acta Haematol 2023; 146 (01) 1-13
  CrossrefPubMedSearch in Google Scholar
• 89 Kelly RJ, Höchsmann B, Szer J. et al. Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2015; 373 (11) 1032-1039
  CrossrefPubMedSearch in Google Scholar
• 90 Zhang B, Chu R, Huang C. et al. Progress in the management of pregnancy with paroxysmal nocturnal hemoglobinuria: a review. J Womens Health (Larchmt) 2024; 33 (01) 98-104
  PubMedSearch in Google Scholar
• 91 Manning JE, Anderson RM, Hill A, Zeidan D, Ciantar E. Pregnancy outcomes in women receiving eculizumab for the management of paroxysmal nocturnal haemoglobinuria. Obstet Med 2022; 15 (01) 45-49
  CrossrefPubMedSearch in Google Scholar
• 92 Giannotta JA, Fattizzo B, Barcellini W. Paroxysmal nocturnal hemoglobinuria in the context of a myeloproliferative neoplasm: a case report and review of the literature. Front Oncol 2021; 11: 756589
  CrossrefPubMedSearch in Google Scholar
• 93 Chatzidavid S, Giannakopoulou N, Diamantopoulos PT. et al. JAK2V617F positive polycythemia vera with paroxysmal nocturnal hemoglobinuria and visceral thromboses: a case report and review of the literature. Thromb J 2021; 19 (01) 16
  CrossrefPubMedSearch in Google Scholar
• 94 Morado M, Freire SandesA, Colado E. et al. PNH working group of the Iberian Society of Cytometry (SIC). Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications. Cytometry B Clin Cytom 2017; Sep; 92 (5) 361-370 . Epub 2016 Oct 1. PMID: 27598686
  CrossrefPubMedSearch in Google Scholar