Abstract
Patients with paroxysmal nocturnal hemoglobinuria (PNH) may present with thrombosis at unusual sites, of which cerebral sinovenous thrombosis (CSVT) is one and screening for PNH is recommended in this condition. Though many patients diagnosed with PNH develop CSVT, it is unclear how many patients with PNH would present for the first time with thrombosis. We analysed the results of screening for PNH by flowcytometry in our patients with CSVT. The laboratory data of patients referred for thrombophilia and PNH testing in CSVT was examined to assess the frequency of PNH at presentation in these patients. FLAER and CD24 on granulocytes and FLAER and CD14 on monocytes respectively were used to screen the leucocytes for PNH by flowcytometry. The data for Protein C, S and Antithrombin deficiency, antiphospholipid antibodies and the Factor V Leiden mutation was examined and circumstantial risk factors were also assessed. Of the 180 cases of CSVT screened by flowcytometry for PNH, not a single case tested positive. Positivity for anti-phospholipid antibodies was the most common thrombophilic risk factor (5%). Pregnancy was the most common circumstantial risk factor. Our data on FLAER based flowcytometry in the North Indian population with CSVT suggests that PNH is not a common risk factor in our patients with thrombosis at this unusual site.
Similar content being viewed by others
References
Bousser MG, Ferro JM (2007) Cerebral venous thrombosis: an update. Lancet Neurol 6:162–170
Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798
Moyo VM, Mukhina GL, Garrett ES, Brodsky RA (2004) Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol 126:133–138
Araten D, Thaler H, Luzzatto L (2005) High incidence of thrombosis in African-American and Latin-American patients with paroxysmal nocturnal haemoglobinuria. Thromb Haemost 93:88–91
Parker CJ (2002) Historical aspects of paroxysmal nocturnal haemoglobinuria: "defining the disease". Br J Haematol 117:3–22
Hillmen P (2000) Implications of recent insights into the pathophysiology of paroxysmal nocturnal haemoglobinuria. Br J Haematol 108:470–479
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV (1995) Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 333:1253–1258
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R et al (2005) Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 106:3699–3709
Wiedmer T, Ando B, Sims PJ (1997) Complement C5b-9 stimulated platelet secretion is associated with a Ca2+ initiated activation of cellular protein kinases. J Biol Chem 262:13674–13681
Hillmen P, Muus P, Dührsen U, Risitano AM, Schubert J, Luzzatto L et al (2007) Effect of the complement inhibitor Ecluzimab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 110:4123–4128
Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR et al (2010) Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom 78:211–230
Sutherland DR, Illingworth A, Marinov I, Ortiz F, Andreasen J, Payne D et al (2018) ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 2: reagent selection and assay optimization for high-sensitivity testing. Cytometry B Clin Cytom 94:23–48
Ahluwalia J, Naseem S, Sachdeva MU, Bose P, Bose SK, Kumar N et al (2014) Paroxysmal Nocturnal Hemoglobinuria is rare cause for thrombosis of the intra-abdominal veins in the ethnic Indian population: results from FLAER-based flowcytometry screening. Eur J Haematol 92:435–443
Garewal G, Das R, Ahluwalia J, Mittal N, Varma S (2003) Prothrombin G20210A is not prevalent in North India. J Thromb Haemost 1:2253–2254
Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67
Illingworth A, Marinov I, Sutherland DR, Wagner-Ballon O, Del Vecchio L (2018) ICCS/ESCCA consensus guidelines to detect GPI deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 3: data analysis, reporting and case studies. Cytometry B Clin Cytom 94:49–66
Meppiel E, Crassard I, de Latour RP, de Guibert S, Terriou L, Chabriat H et al (2015) Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria. a series of 15 cases and review of the literature. Med Baltim 94:1–8
Misra UK, Kalita J, Bansal V, Nair PP (2008) Paroxysmal nocturnal haemoglobinuria presenting as cerebral venous sinus thrombosis. Transfus Med 18:308–311
Narayan D, Kaul S, Ravishankar K, Suryaprabha T, Bandaru VC, Mridula KR et al (2012) Risk factors, clinical profile, and long-term outcome of 428 patients of cerebral sinus venous thrombosis: insights from Nizam's Institute Venous Stroke Registry, Hyderabad (India). Neurol India 60:154–159
Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F (2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 35:664–670
James AH, Bushnell CD, Jamison MG, Myers ER (2005) Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 106:509 – 516
de Latour RP, Mary JY, Salanoubat C, Terriou L, Etienne G, Mohty M et al (2008) Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood 112:3099–3106
Qi X, He C, Han G, Yin Z, Wu F, Zhang Q et al (2013) Prevalence of paroxysmal nocturnal hemoglobinuria in Chinese patients with Budd–Chiari syndrome or portal vein thrombosis. J Gastroenterol Hepatol 28:148–152
Baloda V, Ahluwalia J, Varma N, Chawla YK (2013) Large clones with PNH-type phenotype are not common in patients presenting with intra-abdominal thrombosis–a prospective study. Clin Appl Thromb Hemost 19:562–569
Lee JW, Jang JH, Kim JS, Yoon SS, Lee JH, Kim YK et al (2013) Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry. Int J Hematol 97:749–757
Madkaikar M, Gupta M, Jijina F, Ghosh K (2009) Paroxysmal nocturnal haemoglobinuria: diagnostic tests, advantages, & limitations. Eur J Haematol 83:503–551
Pai N, Ghosh K, Shetty S (2013) Hereditary thrombophilia in cerebral venous thrombosis: a study from India. Blood Coagul Fibrinolysis 24:540–543
Dentali F, Crowther M, Ageno W (2006) Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis. Blood 107:2766–2773
Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B, Cushman M et al (2011) Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:1158–1192
Mercier T, Devos T, Mukovnikova M, Boekx N (2017) Diagnosing nocturnal paroxysmal hemoglobinuria: a single-center 4-year experience. Int J Lab Hem 39:329–336
Connors JM (2017) Thrombophilia testing and venous thrombosis. N Engl J Med 377:1177–1187
Acknowledgements
The help rendered by Dr Harpreet Virk in data retrieval is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The study was approved by Institute Ethics Committee, Postgraduate Institute of Medical Education and Research, Chandigarh, India (IEC no. INT/IEC/2018/EIC001147).
Conflicts of interest
The authors declare that they have no conflicts of interest to declare.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sharma, S., Ahluwalia, J., Atreja, C.B. et al. Screening for paroxysmal nocturnal hemoglobinuria (PNH) in patients presenting with cerebral sinovenous thrombosis (CSVT): Results of a FLAER based flowcytometry study in Indian patients. J Thromb Thrombolysis 49, 584–590 (2020). https://doi.org/10.1007/s11239-019-01982-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11239-019-01982-y