Clinical Features of Disseminated Intravascular Coagulation According to the French-American-British Classification in Patients With Acute Leukemia and Thrombomodulin Alfa Treatment—A Cohort Study Using a Postmarketing Surveillance Database

The aims of this study were to analyze the clinical features of a large number of cases with disseminated intravascular coagulation (DIC) associated with acute leukemia and to assess the safety and efficacy of thrombomodulin alfa (TM-α) using the French-American-British (FAB) classification of hematological malignancies. We retrospectively examined 644 patients with acute leukemia in postmarketing surveillance for TM-α. M3, M2, M4, M1, and M5 subtypes of acute myeloid leukemia (AML) and L2 and L1 subtypes of acute lymphoblastic leukemia (ALL) have been found more frequently among patients with DIC. Bleeding symptoms at baseline were more frequent in M3 and M7 subtypes. Fibrinogen concentrations were lower, and plasmin-plasmin inhibitor complex values were higher in M3 and Philadelphia-positive (Ph+) ALL. Overall DIC resolution rate was 60.2%, higher in L1 and Ph+ ALL, lower in M1, and generally higher in ALL than in AML. Overall survival rate was generally high, at 79.8%, with higher rates in L3, Ph+ ALL, and M3. Regardless of FAB subgroup, TM-α showed improved bleeding symptoms and DIC scores in clinical practice for DIC patients with acute leukemia.

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Clinical Features of DIC According to the French-american-british (FAB) Classification in Patients With Acute Leukemia and Thrombomodulin Alfa Treatment – Cross-sectional Analysis of a Post-marketing Surveillance Study Cohort –

10.21203/rs.3.rs-262863/v1 ◽

2021 ◽

Author(s):

Yoshinobu Seki ◽

Goichi Honda ◽

Noriaki Kawano ◽

Toshimasa Uchiyama ◽

Kazuo Kawasugi ◽

...

Keyword(s):

Acute Leukemia ◽

Clinical Features ◽

Lymphoblastic Leukemia ◽

Study Cohort ◽

Cross Sectional ◽

Safety And Efficacy ◽

Post Marketing Surveillance ◽

Fab Classification ◽

Post Marketing ◽

French American British

Abstract Background: The aims of this study were to analyze the clinical features of a large number of cases with disseminated intravascular coagulation (DIC) associated with acute leukemia, and to clarify the safety and efficacy of thrombomodulin alfa (TM-α) using the French-American-British (FAB) classification of hematological malignancies.Methods: We retrospectively examined 644 patients with acute leukemia in post-marketing surveillance for TM-α.Results: M3, M2, M4, M1, and M5 subtypes of acute myeloid leukemia (AML), and L2 and L1 subtypes of acute lymphoblastic leukemia (ALL) have been found more frequently among patients with DIC. Bleeding symptoms at baseline were more frequent in M3 and M7 subtypes. Fibrinogen concentrations were lower and plasmin-plasmin inhibitor complex values were higher in M3 and Philadelphia-positive (Ph+) ALL. Overall DIC resolution rate was 60.2% with higher rates in L1 and Ph+ ALL, lower in M1, and generally higher in ALL than in AML. The overall survival rate was 79.8%, generally high, with higher survival rates in L3, Ph+ ALL, and M3. In M3 and M7, with high frequencies of pre-existing bleeding, TM-α improved bleeding symptoms. Post-administration DIC scores in each subtype were significantly improved compared with pre-administration scores, except in M6, M7, and MDS-overt AML.Conclusions: This study showed the clinical features of DIC associated with acute leukemia among FAB classifications and also elucidated the safety and efficacy profiles of TM-α by detailed classification based on the FAB classification in clinical practice.Trial registration: The clinical characteristics and treatment outcomes of patients with DIC treated with TM-α between May 2008 and April 2010 were retrospectively analyzed by subgroup analysis of post-marketing surveillance data.

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Increased Soluble Fibrin in Plasma of Patients with Disseminated Intravascular Coagulation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960300900308 ◽

2003 ◽

Vol 9 (3) ◽

pp. 233-240 ◽

Cited By ~ 27

Author(s):

Hideo Wada ◽

Tomohiro Sase ◽

Takeshi Matsumoto ◽

Fumihiko Kushiya ◽

Miho Sakakura ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

Operating Characteristic ◽

Degradation Products ◽

Characteristic Analysis ◽

Soluble Fibrin ◽

Intravascular Coagulation ◽

Hemostatic Markers ◽

Plasmin Inhibitor

Plasma levels of soluble fibrin (SF) were measured in 1184 patients with disseminated intravascular coagulation (DIC) according to Japanese Ministry of Health and Welfare (JMHW) criteria. The usefulness of SF for the diagnosis of DIC was compared with other hemostatic molecular markers. Most hemostatic markers were significantly increased in patients with DIC than in those without DIC. Plasma levels of fibrin and fibrinogen degradation products, thrombin-antihtrombin complex, plasmin-plasmin inhibitor complex, D-dimer, thrombomodulin, and SF levels were also significantly higher in those with pre-DIC than in those without DIC. In classification of overt DIC by International Society of Thrombosis and Haemostasis (ISTH) criteria, most hemostatic markers were significantly increased in patients with overt DIC than in those without overt DIC. Plasma levels of SF 'in patients with DIC were significantly higher than those in patients with pre-DIC, which were significantly higher than in those without DIC. Plasma levels of SF were also significantly higher in patients with overt DIC than in those with non-overt DIC. The correlation between plasma SF levels and DIC score according to JMHW criteria or ISTH criteria was good. Receiver operating characteristic analysis shows that SF was the best marker for the diagnosis of DIC or overt DIC. These findings suggest that plasma SF might be useful marker for the diagnosis of DIC or overt DIC.

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Classifying acute leukemia by immunophenotyping: a combined FAB- immunologic classification of AML

Blood ◽

10.1182/blood.v68.6.1355.1355 ◽

1986 ◽

Vol 68 (6) ◽

pp. 1355-1362 ◽

Cited By ~ 104

Author(s):

PB Neame ◽

P Soamboonsrup ◽

GP Browman ◽

RM Meyer ◽

A Benger ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Gold Standard ◽

Lymphoblastic Leukemia ◽

Myelogenous Leukemia ◽

Fab Classification ◽

Acute Myelogenous ◽

French American British

Abstract A panel of commercially available monoclonal antibodies and five heteroantisera were used to distinguish and subtype 138 cases of acute leukemia (AL). The immunophenotype was compared with the French- American-British (FAB) classification obtained on the cases. The immunophenotype discriminated acute myelogenous leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognized cases not distinguished by cytochemistry (22% of cases), mixed lineage phenotypes (13% of cases), and cases with separate populations of lymphoblasts and myeloblasts (one case). Using the immunologic panel and derived criteria to subtype AML, correspondence of the immunophenotype to the FAB subtypes M1, M2, M4, and M5 was possible in greater than 80% of cases. A combined classification of the immunophenotype and FAB morphology/cytochemistry was devised for AML subtyping. It is recommended that immunophenotyping should be done at least in all cases with negative orinconclusive cytochemistry. At present, we suggest that until a “gold standard” for identifying leukemic subtypes is developed, the best method for typing acute leukemia is by using a combination of morphology, cytochemistry and immunophenotyping.

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Classifying acute leukemia by immunophenotyping: a combined FAB- immunologic classification of AML

Blood ◽

10.1182/blood.v68.6.1355.bloodjournal6861355 ◽

1986 ◽

Vol 68 (6) ◽

pp. 1355-1362

Author(s):

PB Neame ◽

P Soamboonsrup ◽

GP Browman ◽

RM Meyer ◽

A Benger ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Gold Standard ◽

Lymphoblastic Leukemia ◽

Myelogenous Leukemia ◽

Fab Classification ◽

Acute Myelogenous ◽

French American British

A panel of commercially available monoclonal antibodies and five heteroantisera were used to distinguish and subtype 138 cases of acute leukemia (AL). The immunophenotype was compared with the French- American-British (FAB) classification obtained on the cases. The immunophenotype discriminated acute myelogenous leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognized cases not distinguished by cytochemistry (22% of cases), mixed lineage phenotypes (13% of cases), and cases with separate populations of lymphoblasts and myeloblasts (one case). Using the immunologic panel and derived criteria to subtype AML, correspondence of the immunophenotype to the FAB subtypes M1, M2, M4, and M5 was possible in greater than 80% of cases. A combined classification of the immunophenotype and FAB morphology/cytochemistry was devised for AML subtyping. It is recommended that immunophenotyping should be done at least in all cases with negative orinconclusive cytochemistry. At present, we suggest that until a “gold standard” for identifying leukemic subtypes is developed, the best method for typing acute leukemia is by using a combination of morphology, cytochemistry and immunophenotyping.

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Management of Disseminated Intravascular Coagulation in Acute Leukemias

Hämostaseologie ◽

10.1055/a-1393-8302 ◽

2021 ◽

Vol 41 (02) ◽

pp. 120-126

Author(s):

Hugo ten Cate ◽

Avi Leader

Keyword(s):

Acute Leukemia ◽

Disseminated Intravascular Coagulation ◽

Degradation Products ◽

Lymphoblastic Leukemia ◽

Scoring Systems ◽

Underlying Disease ◽

Clinical Consequence ◽

Blood Products ◽

Acute Leukemias ◽

Intravascular Coagulation

AbstractDisseminated intravascular coagulation (DIC) is characterized by the intravascular activation of coagulation with loss of localization arising from different causes, and is diagnosed using scoring systems which rely upon the presence of an underlying disorder compatible with DIC alongside hemostatic derangements such as low platelet count, prolonged prothrombin time, and elevated fibrinogen degradation products. DIC is common in patients with acute leukemia, with prevalence ranging from 17 to 100% in acute promyelocytic leukemia (APL) and 8.5 to 25% in acute lymphoblastic leukemia (ALL) and non-APL acute myeloid leukemia (AML). The pathophysiology is complex and varies between the leukemia subtypes, and is not fully reflected by the laboratory markers currently used to classify DIC. Similarly, the clinical consequence of DIC in acute leukemia also varies across the types of leukemia. DIC is primarily associated with bleeding in APL, while thrombosis is the dominant phenotype in ALL and non-APL AML. The cornerstone of managing DIC is the treatment of the underlying disease, as exemplified by the important role of early administration of all-trans retinoic acid in APL. Other aspects of management focus on supportive care aimed at minimizing the risk of bleeding, via transfusion of blood products. The use of blood products is more liberal in APL, due to the hemorrhagic phenotype and unacceptably high rates of early hemorrhagic death. This review will focus on the pathophysiology, risk factors, clinical implications, and the management of DIC in patients across the spectrum of acute leukemias.

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Acute Leukemia

10.2310/im.1247 ◽

2016 ◽

Author(s):

Richard A. Larson ◽

Roland B Walter

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Myeloid Leukemia ◽

Who Classification ◽

Lymphoblastic Leukemia ◽

World Health ◽

Acute Leukemias ◽

Acute Myeloid

The acute leukemias are malignant clonal disorders characterized by aberrant differentiation and proliferation of transformed hematopoietic progenitor cells. These cells accumulate within the bone marrow and lead to suppression of the production of normal blood cells, with resulting symptoms from varying degrees of anemia, neutropenia, and thrombocytopenia or from infiltration into tissues. They are currently classified by their presumed cell of origin, although the field is moving rapidly to genetic subclassification. This review covers epidemiology; etiology; classiﬁcation of leukemia by morphology, immunophenotyping, and cytogenetic/molecular abnormalities; cytogenetics of acute leukemia; general principles of therapy; acute myeloid leukemia; acute lymphoblastic leukemia; and future possibilities. The figure shows the incidence of acute leukemias in the United States. Tables list World Health Organization (WHO) classification of acute myeloid leukemia and related neoplasms, expression of cell surface and cytoplasmic markers for the diagnosis of acute myeloid leukemia and mixed-phenotype acute leukemia, WHO classification of acute lymphoblastic leukemia, WHO classification of acute leukemias of ambiguous lineage, WHO classification of myelodysplastic syndromes, European LeukemiaNet cytogenetic and molecular genetic subsets in acute myeloid leukemia with prognostic importance, cytogenetic and molecular subtypes of acute lymphoblastic leukemia, terminology used in leukemia treatment, and treatment outcome for adults with acute leukemia. This review contains 1 highly rendered figure, 9 tables, and 117 references.

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High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia [see comments]

Blood ◽

10.1182/blood.v79.5.1305.1305 ◽

1992 ◽

Vol 79 (5) ◽

pp. 1305-1310 ◽

Cited By ~ 47

Author(s):

AH Sarris ◽

S Kempin ◽

E Berman ◽

J Michaeli ◽

C Little ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Disseminated Intravascular Coagulation ◽

De Novo ◽

Sinus Thrombosis ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Temporal Association ◽

Remission Induction ◽

Time Interval ◽

Intravascular Coagulation

Abstract We determined the incidence and complications of disseminated intravascular coagulation (DIC) at presentation and during remission induction of previously untreated adults with acute lymphoblastic leukemia (ALL) or de novo Philadelphia chromosome-positive ALL (PCALL) seen at Memorial Hospital between January 1, 1978 and December 31, 1989. DIC was diagnosed in the presence of (1) low fibrinogen (less than or equal to 160 mg/dL), (2) prolonged prothrombin time (PT) and falling fibrinogen, or (3) prolonged PT and positive fibrin split products (FSP). L-Asparaginase was not used during remission induction. Among adequately screened patients with ALL, DIC was detected in 7 of 58 (12%) before initiation of chemotherapy and in 35 of 45 (78%) during remission induction. DIC was not simply the result of infection because clinical and laboratory signs of infection were absent in 16 patients, whereas only 2 of the 22 febrile patients with DIC had positive cultures. Among the 38 patients with DIC at presentation or during remission induction, serious complications were seen in 13 in temporal association with DIC (pulmonary embolus in one, sagittal sinus thrombosis in three, and serious hemorrhage in nine) and were major factors in the deaths of three patients. Among the 10 patients with thorough screening but no evidence of DIC there was only one hemorrhage during the same time interval. In patients with PCALL, DIC was detected in 9% at presentation and in 80% during remission induction. We conclude that DIC is rare at presentation but common during remission induction of adult ALL and PCALL and may be associated with significant thrombotic and hemorrhagic complications. We suggest daily screening for DIC during the first 14 days of remission induction. The treatment of DIC in ALL and PCALL should be a subject of future clinical studies.

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Circulating intranuclear proteins may play a role in development of disseminated intravascular coagulation in individuals with acute leukemia

International Journal of Hematology ◽

10.1007/s12185-019-02798-5 ◽

2019 ◽

Vol 111 (3) ◽

pp. 378-387 ◽

Cited By ~ 3

Author(s):

Kayo Harada-Shirado ◽

Xintao Wang ◽

Hirotaka Mori ◽

Masahiko Fukatsu ◽

Hiroshi Takahashi ◽

...

Keyword(s):

Acute Leukemia ◽

Disseminated Intravascular Coagulation ◽

Intravascular Coagulation

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Simultaneous or sequential expression of lymphoid and myeloid phenotypes in acute leukemia

Blood ◽

10.1182/blood.v65.1.142.142 ◽

1985 ◽

Vol 65 (1) ◽

pp. 142-148 ◽

Cited By ~ 79

Author(s):

PB Neame ◽

P Soamboonsrup ◽

G Browman ◽

RD Barr ◽

N Saeed ◽

...

Keyword(s):

Acute Leukemia ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Lymphoblastic Leukemia ◽

Differentiation Markers ◽

Lymphoid Leukemia ◽

Chromosome Marker ◽

Fab Classification ◽

Blast Cells ◽

French American British

Abstract Acute mixed myeloid-lymphoid leukemia is uncommon. We report four cases in which myeloid and lymphoid cell markers were observed simultaneously or sequentially when 94 patients with acute leukemia were phenotyped according to the French-American-British (FAB) classification system, with cytochemical stains, and with immunologically defined differentiation markers (identified by monoclonal antibodies and antiterminal deoxynucleotidyl transferase [TdT]). In one case, conversion from acute lymphoblastic leukemia to acute myeloid leukemia was noted (FAB L1, TdT+ to FAB M4, Auer rods, TdT-). In another patient, two distinct populations of myeloid and lymphoid blast cells were observed simultaneously (TdT-, LeuM1+/TdT+, LeuM1-). In two additional patients, acute leukemia was characterized by the expression of both lymphoid and myeloid markers on the same cell (TdT+/Leu M1+, B4+/Leu M1+ and greater than or equal to 70% TdT+, T11+, My9+). The Philadelphia (Ph1) chromosome was negative in all cases, though other chromosomal abnormalities were noted in three out of four cases. Malignant transformation of a pluripotential stem cell for both lymphoid and myeloid lineages, with or without the Ph1 chromosome marker, could explain the coexistence of distinct populations of lymphoblasts and myeloblasts in acute leukemia. Acute leukemia with a biphenotypic profile may reflect genome depression accompanying neoplasia.

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