Background: Philadelphia-negative myeloproliferative disorders (Ph-MPD) are common causes of unusual splanchnic or cerebral vein thrombosis, which is treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Heparin-induced thrombocytopenia (HIT) is a dangerous potential complication of this therapy, but it has rarely been reported in Ph-MPD. Patients and Methods: We retrospectively reviewed clinical records of 29 patients with Ph-MPD who have been treated with UFH or LMWH for unusual splanchnic or cerebral vein thrombosis (3 cerebral sinus, 6 portal and 20 hepatic vein). The goal of the study was to determine the occurrence of new thrombotic events during heparin therapy secondary to HIT (HITT). Results: During heparin therapy, 5 out of the 29 patients (17%) developed a new thrombotic episode (pulmonary embolism) with a high clinical probability of HIT based on the 4 T’s score even though not all the patients developed ‘true’ thrombocytopenia. A diagnosis of HIT was established in 2 patients (6.8%) through the presence of heparin-related antibodies. Conclusions: Ph-MPD patients on heparin warrant careful monitoring and HIT has to be suspected whenever platelet counts drop or a new thrombosis is detectable.

Keywords:
Essential thrombocythemia, Polycythemia vera, JAK2 mutation, Unusual splanchnic or cerebral vein thrombosis, Heparin-induced thrombocytopenia
1.
Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR, Cancer Genome Project: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054–1061.
2.
Elliott MA, Tefferi A: Thrombosis and hemorrhage in polycythemia vera and essential thrombocythemia. Br J Haematol 2005;128:275–290.
3.
Vannucchi AM, Barbui T: Thrombocytosis and thrombosis. Am Soc Hematol 2007:363–370.
4.
Denninger MH, Chait Y, Casadevall N, Hillaire S, Guillin MC, Bezeaud A, Erlinger S, Briere J, Valla D: Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology 2000;31:587–591.
5.
Randi ML, Stocco F, Rossi C, Tison T, Girolami A: Thrombosis and hemorrhage in thrombocytosis: evaluation of a large cohort of patients (357 cases). J Med 1991;22:213–223.
6.
Briere JB: Budd-Chiari syndrome and portal vein thrombosis associated with myeloproliferative disorders: diagnosis and management. Semin Thromb Hemostas 2006;32:208–218.
7.
Warkentin TE: Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol 2003;121:535–555.
8.
Warkentin TE, Roberts RS, Hirsh J, Kelton JG: An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med 2003;163:2518–2524.
9.
Spectre G, Kalish Y, Schliamser L, Varon D: Heparin-induced thrombocytopenia in myeloproliferative disorders: a rare underdiagnosed complication? Am J Hematol 2008;83:420–423.
10.
Murphy S, Iland H, Rosenthal D, Lazlo J: Essential thrombocythemia: clinical and laboratory characteristics at presentation. Semin Hematol 1986;23:177–192.
11.
Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;14:2292–2202.
12.
Randi ML, Putti MC, Scapin M, Pacquola E, Tucci F, Micalizzi C, Zanesco L, Fabris F: Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood 2006;108:3600–3602.
13.
Lo GK, Juhl D, Warkentin TE, Lo GK, Juhl D, Warkentin TE: Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Hemostas 2006;4:759–765.
14.
Eichler P, Budd U, Haas S, Kroll H, Loreth RM, Meyer O, Pachmann U, Pötzsch B, Schabel A, Albrecht D, Greinacher A: First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4/Heparin ELISA. Thromb Haemostas 1999;81:625–629.
15.
Levine R, McCollum D, Hursting MJ: How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia? Chest 2006;130:681–687.
16.
Warkentin TE: Think of HIT when thrombosis follows heparin. Chest 2006;130:631–632.
17.
Prandoni P, Siragusa S, Girolami B, Fabris F, Belzoni investigators group: The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study. Blood 2005;106:3049–3054.
18.
Warkentin TE, Kelton JG: A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996;101:502–507.
19.
Pouplard C, May MA, Regina S, Marchand M, Fusciardi J, Gruel Y: Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br J Haematol 2005;128:837–841.
20.
Plessier A, Consigny Y, Rautou PE, Boucari R, Bezeaud A, Boudaoud L, Kiladjian JJ, Brumpt C, Saada V, Condat B, Valla DC, Denninger MH: Budd Chiari syndrome (BCS) and heparin-induced thrombocytopenia (HIT) (abstract). J Hepatol 2006;S92.
21.
Valla D: The diagnosis and management of the Budd-Chiari syndrome: consensus and controversies. Hepatology 2003;38:793–803.
22.
Kitchens CS: Thrombocytopenia due to acute venous thromboembolism and its role in expanding the differential diagnosis of heparin-induced thrombocytopenia. Am J Hematol 2004;76:69–73.
© 2010 S. Karger AG, Basel
2010
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.