Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells.
Mast cells (MC) are multipotent hemopoietic effector cells producing diverse mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase+ MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plasmin-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD117/c-kit+, CD123/IL-3R alpha-, CD11b/C3biR-), biochemical analysis (cellular ratio [ng:ng] of tryptase to histamine >1), and electron microscopy. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 30% diffusely scattered MC, and a complex karyotype. No dense, compact MC infiltrates (mastocytosis) were detectable in bm sections. Despite hyperfibrinolysis and mediator syndrome (flushing, headache), the patient received remission induction polychemotherapy (DAV) followed by two cycles of consolidation with intermediate dose ARA-C (2 x 1 g/m2/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without evidence of recurring MDS. Moreover, in response to chemotherapy, the hyperfibrinolysis and mediator syndrome resolved, and the circulating c-kit+ MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement.
Wimazal
F
F
Department of Internal Medicine I, University of Vienna, Austria.
Sperr
W R
WR
Horny
H P
HP
Carroll
V
V
Binder
B R
BR
Fonatsch
C
C
Walchshofer
S
S
Födinger
M
M
Schwarzinger
I
I
Samorapoompichit
P
P
Chott
A
A
Dvorak
A M
AM
Lechner
K
K
Valent
P
P
D000368:Aged; D001777:Blood Coagulation; D001853:Bone Marrow / Q000473:pathology; D053818:Chymases; D004247:DNA / Q000032:analysis; D005342:Fibrinolysis; D019084:Fluorescent Antibody Technique, Indirect; D006632:Histamine / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007621:Karyotyping; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D008854:Microscopy, Electron; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000473:pathology*; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012697:Serine Endopeptidases / Q000032:analysis; D053802:Tryptases
D006632:Histamine; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases