SYTHROM Cohort, Myeloproliferative Neoplasia With Normal CBC and Thrombotic Complications

Among the etiologies of thrombosis, myeloproliferative neoplasia (MPN) is quite rare but should be investigated in case of thrombosis of atypical localization (digestive or cerebral) or in the context of recurrent idiopathic thrombosis in a young subject. Thrombosis could reveal an underlying MPN through the identification of a JAK2 V617F mutation. Rarely, MPN with thrombotic complications present with normal complete blood count(CBC). In case of a MPN with a thrombotic event but without CBC abnormality, anti-thrombotic treatment is recommended. But there is no recommendation for the indication of cytoreductive therapy and the clinician's decision is often empirical. One of the major complications of for essential thrombocythemia (ET) or polycythemia vera (PV) is thrombosis and an age over 60 is a major risk factor. The treatment of thrombosis associated with TE or PV is based on recommendations the main therapeutic objective of which is to reduce the thrombotic risk. The combination of a cytoreducing agent and antithrombotic treatment is thus proposed in high-risk patients. The efficacy of this management is monitored by assessing CBC with the objective of normalization at \<400 G/L of platelets for ET patients and \<45% hematocrit in case of PV. The absence of abnormal CBC makes it difficult to justify cytoreduction. The benefit of such a therapy in this context has not been clinically demonstrated. If a cytoreductive therapy is initiated, no biological parameters are available to assess the response to treatment. The objective of this observational study is to evaluate the incidence of recurrence of thrombosis in patients whose thrombotic event revealed an underlying MPN with normal CBC. A comparison of groups treated or not with cytoreductive agents will be performed. Longitudinal monitoring of the patients will provide a better understanding of the nature and kinetics of hematological changes in these patients.

Sex

All

Minimum age

18 Years

Inclusion Criteria :

* Adult ≥18 years old
* Diagnosis of a deep arterial or venous thrombotic event verified by imaging (Doppler or CT scan)
* Diagnosis of MPN with normal CBC according to WHO 2017 criteria characterized by the detection of a molecular abnormality JAK2V617F mutation (regardless of allelic load), CALR or MPL and/or a bone marrow biopsy with abnormalities in favor of MPN.
* Normal blood cell count not suggestive of polycythemia vera (hematocrit\<48% and hemoglobin\<16g/dL for women; hematocrit\<49% and hemoglobin\<16.5g/dL for men), essential thrombocythemia (platelets\<450 G/L) nor myelofibrosis (white blood cell count\<11 G/L, no anemia or erythromyelemia associated with splenomegaly) at the time of the thrombotic event.

Exclusion Criteria :

* Minors (\<18 years of age)
* Microcirculation disorders (erythromelalgia, headaches, paresthesia, ischemia of the extremities)
* Superficial or deep arterial or venous thrombosis NOT verified by imaging
* Diagnosis or history of TE, PV or myelofibrosis at time of first thrombotic event
* Diagnosis of mixed myelodysplastic/myeloproliferative syndrome
* Diagnosis of unclassifiable MPN with excess blasts at the onset or signs of myelodysplasia as defined by the WHO 2017 classification

• BACKGROUNDKiladjian JJ, Cervantes F, Leebeek FW, Marzac C, Cassinat B, Chevret S, Cazals-Hatem D, Plessier A, Garcia-Pagan JC, Darwish Murad S, Raffa S, Janssen HL, Gardin C, Cereja S, Tonetti C, Giraudier S, Condat B, Casadevall N, Fenaux P, Valla DC. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008 May 15;111(10):4922-9. doi: 10.1182/blood-2007-11-125328. Epub 2008 Feb 4. PMID 18250227
• BACKGROUNDDe Stefano V, Fiorini A, Rossi E, Za T, Farina G, Chiusolo P, Sica S, Leone G. Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost. 2007 Apr;5(4):708-14. doi: 10.1111/j.1538-7836.2007.02424.x. Epub 2007 Jan 29. PMID 17263783
• BACKGROUNDLevraut M, Legros L, Drappier C, Bene MC, Queyrel V, Raynaud S, Martis N. Low prevalence of JAK2 V617F mutation in patients with thrombosis and normal blood counts: a retrospective impact study. J Thromb Thrombolysis. 2020 Nov;50(4):995-1003. doi: 10.1007/s11239-020-02100-z. PMID 32266587
• BACKGROUNDBarbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, Rodeghiero F, d'Amore ES, Randi ML, Bertozzi I, Marino F, Vannucchi AM, Antonioli E, Carrai V, Gisslinger H, Buxhofer-Ausch V, Mullauer L, Carobbio A, Gianatti A, Gangat N, Hanson CA, Tefferi A. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011 Aug 10;29(23):3179-84. doi: 10.1200/JCO.2010.34.5298. Epub 2011 Jul 11. PMID 21747083
• BACKGROUNDBarbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012 Dec 20;120(26):5128-33; quiz 5252. doi: 10.1182/blood-2012-07-444067. Epub 2012 Oct 1.