A 37-year-old female patient with systemic mastocytosis who was admitted with severe unexplained bleeding symptoms is studied. Laboratory procedures established the diagnosis of a patient-derived—heparin-like anticoagulant as a very rare hemostatic abnormality predisposing to bleeding. The patient died from refractory disease despite therapy with protamine, initiation of chemotherapy, and supportive measures. The case illustrates the clinical presentation and diagnosis of heparin-like anticoagulants. Etiology, pathophysiology, and therapeutic options are discussed.
Hartmann K., Henz BMMastocytosis: recent advances in defining the disease. Br J Dermatol. 2001;144:682-695.
2.
Delling G., Ritzel H., Wener M.Histologische Charakteristika und Häufigkeit der sekundären Osteoporose bei systemischer Mastozytose. Pathologie. 2001 ; 22:132-140.
3.
Valent P., Horny HP, Li C., et al. Mastocytosis (mast cell disease). In: Jaffe ES, Harris NL, Stein H, Cardiman JW , eds. World Health Organization (WHO) classification of tumours. Pathology Genetics. Tumours of Haemoatopoietic and lymphoid tissues . Geneva, Switzerland: WHO; 2001: 291-302.
4.
Tefferi A., Pardanani A.Clinical, genetic, and therapeutic insights into systemic mast cell disease . Curr Opin Hematol. 2004;11:58-64.
5.
Tefferi A., Pardanani A.Systemic mastocytosis: current concepts and treatment advances. Curr Hematol Rep. 2004;3:197-202.
6.
Valent P., Akin C., Sperr WR, et al. Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol. 2003;122:695-717.
7.
Crivellato E. , Beltrami CA, Mallardi F., et al. The mast cell; an active participant or an innocent bystander. Histol Histopathol. 2004;19:259-270.
8.
Ruggiero M., Melli M., Parma B., Bianchini P., Vannucchi S.Isolation of endogenous anticoagulant N-sulfated glycosaminoglycans in human plasma from healthy subjects. Pathophysiol Haemost Thromb . 2002;32:44-49.
9.
Bussel JB, Steinherz PG, Miller DR, Hilgartner MWA heparin-like anticoagulant in an 8-month-old boy with acute monoblastic leukemia. Am J Pathol. 1984;16:83-90.
10.
Horne MK III, Chao ES, Wilson OJ, Scialla SJ, Lynch MA, Kragel PJA heparin-like anticoagulant as part of global abnormalities of plasma glycosaminoglycans in a patient with transitional cell carcinoma. J Lab Clin Med. 1991;118:250-260.
11.
Palmer RN, Rick ME, Rick PD, Zeller JA, Gralnick MDCirculating heparan sulfate anticoagulant in a patient with a fatal bleeding disorder. N Engl J Med. 1984; 310:1696-1699.
12.
Garnier G., Taillan B., Castanet J., Pesce A., Dujardin P.Heparin-like anticoagulant in small cell bronchial carcinoma. Rev Med Interne. 1991;12:213-214.
13.
Llamas P., Outeirino J., Espinoza J., Santos AB, Roman A., Tomas JFReport of three cases of circulating heparin-like anticoagulants. Am J Hematol. 2001;67:256-258.
14.
Hill GR, Hickton CM, Brennan SO, Atkinson CH, Heaton DCAcquired heparin-like anticoagulants: a second case in metastatic breast carcinoma and literature review. Clin Lab Haematol. 1996;18:291-295.
15.
Goihman Yahr M., Goldstein C., Gonzalez Y., et al. A clinical constellation in disuse: vitiligo, mastocytosis of the bone marrow, circulating heparinoid, chronic leg ulcer, hypoalbuminemia, ulcerative colitis and hepatic fibrosis. Med Cutan Ibero Lat Am. 1977;5:229-234.
Nenci GG, Berrettini M., Parise P., Agnelli G.Persistent spontaneous heparinaemia in systemic mastocytosis. Folia Haematol Int Mag Klin Morphol Blutforsch. 1982; 109:453-463.
18.
Smith TF, Welch TR, Allen JB, Sondheimer JMCutaneous mastocytosis with bleeding: probable heparin effect. Cutis. 1987;39:241-244.
19.
Hansen U., Wiese R., Knolle J.Shock and coagulation disorders in systemic mastocytosis. Dtsch Med Wochenschr. 1994;119:1231-1234.
20.
Tefferi A., Nichols WL, Bowie EJCirculating heparin-like anticoagulants: report of five consecutive cases and a review. Am J Med. 1990;88:184-188.
21.
Tefferi A., Owen BA, Nichols WL, Witzig TE, Owen WGIsolation of a heparin-like anticoagulant from the plasma of a patient with metastatic bladder carcinoma. Blood. 1989;74:252-254.
22.
Wages DS, Staprans I., Hambleton J., Bass NM, Corash L.Structural characterization and functional effects of a circulating heparan sulfate in a patient with hepatocellular carcinoma. Am J Hematol . 1998;58:285-292.
23.
Horne MK III, Chao ES, Wilson OJHeparin-like anticoagulant associated with systemic candidiasis. Am J Hematol. 1990;35:37-44.
24.
Lasser EC, Simon RA, Lyon SG, Hamblin AE, Stein R.Heparin-like anticoagulants in asthma. Allergy. 1987; 42:619-625.
25.
Cassese E., Piscitelli V., Di Grazia F., Di Prisco L., Balbi C., Balbi GCHeparin-like factors in pregnancy. Report of a clinical case. Minerva Ginecol. 1998;50:435-440.
Jarosova A. , Filip V., Monhart V., Limberk B.Circulating heparin-like anticoagulant-2 cases of successful therapy. Vnitr Lek. 1992;38:513-517.
28.
Hauswirth AW , Simonitsch-Klupp I., Uffmann M., et al. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. Leuk Res. 2004;28:249-257.
29.
Worobec ASTreatment of systemic mast cell disorders. Hematol Oncol Clin North Am. 2000;14:659-687.
30.
Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, Van `t Wout JW, Verhoef G., Gerrits WB, van Dobbenburgh OA, Pasmans SG, Fijnheer R.Cladribine therapy for systemic mastocytosis. Blood. 2003;102:4270-4276.
31.
Akin C., Fumo G., Avuz AS, Lipsky PE, Neckers I., Metcalfe DDA novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood. 2004;103:3222-3225.
