The authors have declared that no competing interests exist.
Acute leukaemia are the clonal and malignant proliferation of immature hematopoietic cells (blast), blocked in their differentiation process. There is an interaction between cancer cells and the clotting process. This could be the expression of Tissue Factor (TF) on the surface of tumor cells; or a lesion of the vascular endothelium and platelet activation. The result is an activation of clotting that can lead to disseminated Intravascular Coagulation (DIC). The objective of this study was to assess the risk of DIC occurring in patients with acute leukaemia.
This was a cross-sectional study for analytical purposes that took place on 40 frozen samples from the biobank of the haematology laboratory of Teaching Hospital Yopougon for which the diagnosis of acute leukaemia had been taken from myelogram. The myelogram results were accompanied by hemogram data. PTTa, QT, fibrinogen and D-Dimers were performed on these samples. The risk assessment of DIC occurred was determined on the recommendations of the International Society of Thrombosis and Hemostasis (ISTH).
We noted a female predominance with a Sex Ratio (M / F) of 0.90. The average age of the patients was 38 years (± 23 years) with extremes ranging from 2 to 84 years. ALL represented 20 % of cases against 80 % for AMLs. Hemogram parameters were characterized by severe anaemia (Tx Hb < 6 g / dL) in 52.5 % of cases; hyperleukocytosis > 100.103 / mm3 in 35 % of cases; thrombocytopenia < 25.103 / mm3 in 40 % of case; and significant blood and spinal cord blastosis (> 80 %). The lengthening of the PTTa was observed in 50 % of cases, compared to 40% for the QT. Similarly, hyperfibrinemia was present in 65% of cases. D-Dimers were high in almost all subject (95 % of cases). According to the ISTH criteria, 17.5 % of subjects were at risk of developing a DIC.
The risk of occurrence of DIC is indeed present during acute leukaemia. The parameters of haemostasis are thus found to be crucial data in the follow-up assessment during the diagnosis of acute leukaemia.
Acute leukeamia (AL) is the clonal and malignant proliferation strains of immature hematopoietic cells, which are blocked in their differentiation process, which invade the bone marrow then the peripheral blood and finally other organs. They are characterized by at least 20 % infiltration of blast
During AL, hyperleukocytosis (> 50.103 / mm3) represents an emergency situation and the latter may be associated with leukostasis syndrome
DIC is a systemic pathophysiologic process and not a single disease entity, resulting from an overwhelming activation of coagulation that consumes platelets and coagulation factors and causes microvascular fibrin and thrombin, which can result in multiorgan dysfunction syndrome
Many studies have already established the relationship between DIC and acute promyelocyte leukaemia 9-12. But what could be the risk of DIC occurring during other types of acute leukaemia? We have therefore set ourselves the general goal of studying hypercoagulability in acute leukaemia in Abidjan.
This was a descriptive cross-sectional study with an analytical focus; which took place from September to October 2019 in the Hematology Unit of the Central Laboratory of the Teaching Hospital of Yopougon and the National Institute of Public Health; due to the accessibility of technical equipment. The study population was represented by frozen samples from the biobank of the haematology Unit of the Central Laboratory of Yopougon. Samples for which the diagnosis of acute leukaemia was made at myelogram were selected for the study. For each of these samples, the myelogram results were accompanied by the hemogram data. A total of forty samples were selected for the study. The analyses were carried out on the Sysmex CA 600 series coagulation automaton.
The parameters studied were the partial thromboplastin time with activator (normal values: Patient / control ratio < 1.2), the Quick time (normal values: 9.1 -12.3 seconds), fibrinogen (normal values: 2 - 4 g / L) and D-Dimers (normal values < 500 ng / mL). The risk of DIC occurring has been determined according to the recommendations of the International Society of Thrombosis and Haemostasis (
Parameters | Values | Score |
Quick Time | ≥ 3 sec | 1 |
≥ 6 sec | 2 | |
Fibrinogen | ≤ 1 g/L | 1 |
D-Dimers | >500 ng/mL | 2 |
Platelets | ≤ 100.10³/mm³ | 1 |
≤ 50 .10³/mm³ | 2 |
If Score ≥ 5: Risk of disseminated Intravascular Coagulation If Score <5: No risk of disseminated Intravascular Coagulation
Statistical analyzes were performed with XLSTAT 2014 and EPI INFO version 7.2 software for Windows®. The test results of the parameters studied were reported as an average (± standard deviation). The comparison of quantitative variables was carried out with the exact Fischer-Snedecor test. The comparison of the means was carried out using Student's t tests.
The Sex Ratio M / F was 0.9; while the most represented age group was 20 to 40 years old with 30% of cases. Clinically, tumor syndrome was present in 45% of cases.
Average | SD | Min | Max | |
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hemoglobin level (g/dL) | 7 | 2.7 | 3.4 | 14.4 |
WBC (103/mm3) | 103.7 | 151.1 | 0.9 | 634 |
Platelets (103/mm3) | 73.2 | 114.2 | 5.8 | 690 |
Peripheral Balsts (%) | 64.5 | 20.6 | 22.0 | 92 |
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Spinal Blasts (%) | 57 | 22.9 | 23.0 | 97 |
We reported hyperleukocytosis greater than 100.103/mm3 in 35% of cases, while 87.5 % of subjects had thrombopenia. From a cytologic point of view, we observed 80 % of AMLs versus 20 % of ALLs. Within the myeloid lineage, AML 1 came first with 37.5 %, while ALL 2 came first in the lymphoid lineage with 15 % of cases.
At haemostasis, a prolongation of the PTTa was observed in 50 % of cases and a prolongation of the QT in 40 % of the cases. D-dimers were high in 95 % of subjects, while only 65 % of subjects had fibrinogen elevation.
Average | SD | Min | Max | |
PTTa (seconds) | 32.6 | 16.0 | 19.8 | 103 |
QT (seconds) | 13.07 | 2.26 | 10 | 21.7 |
FIBRINOGEN (g/L) | 5.3 | 1.8 | 2.1 | 8.8 |
D-DIMERS (ng/mL) | 3769 | 2947 | 404 | 8945 |
According to the ISTH criteria, only 17.5 % of subjects were at risk of developing a DIC.
Type of leukaemia | DIC workforce / Total workforce |
ALL 1 | 0/2 |
ALL 2 | 1/6 |
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AML 0 | ¼ |
AML 1 | 2/15 |
AML 2 | 2/11 |
AML 3 | 1/1 |
AML 5 | 0/1 |
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(
Parameters | DIC risk present | DIC risk absent | p Value (α = 5 %) |
Age (average) | 40 | 38 | 0,8 |
Sex: M/F (workforce) | 2/5 | 17/16 | 0,4 |
hemoglobin level g/dL (average) | 7,3 | 7 | 0,8 |
WBC 103/mm3 (average) | 180,6 | 87,4 | 0,3 |
Spinal Blasts (%) (average) | 63,1 | 64,8 | 0,9 |
Peripheral Balsts % (average) | 56 | 57,2 | 0,9 |
PTTa seconds (average) | 33,1 | 32,4 | 0,5 |
The global burden of cancer has now reached 18.1 million new cases and 9.6 million deaths in 2018. In Africa, particularly in Ivory Coast, the incidence of AL is increasing and according to Globocan
The AL hemogram showed hyperleukocytosis with an average white blood cell count of 103,000 / mm3. Important hyperleukocytosis (> 100,000 / mm3) was observed in 35 % of patients. This result is different from those obtained by Lachachi and Jmili & al.
Observation of different peripheral blood smears had reported peripheral blastosis in 100 % of cases. This result is in perfect agreement with those obtained by Lachachi (93.9 %) as well as Jmili & al. (92 %)
Cytology has shown a predominance of acute myeloid leukaemia (80 %) and 20% of acute lymphoid leukaemia. These results are in agreement with those obtained by Lachachi
At haemostasis, a prolongation of the PTTa was observed in 50 % of cases and an extension of the QT in 40 % of cases. These results are different from those of Dixit & al.
Cancer cells can interact with clotting processes both directly and indirectly. The direct route could be the expression of TF on the surface of the tumor cell. The result would the formation of a procoagulant cancer cell, which would cause the direct activation of the X-factor. Many authors have shown that a high proportion of patients with acute leukaemia have a clotting abnormality at the time of diagnosis. This would contribute to both the thrombotic tendency and the bleeding.
The risk of occurrence of Disseminated Intravascular Coagulation was present in 17.5 % of cases. This result is different from that obtained by Dixit & al. and Yanada & al who observed values of 14.9 % and 29 % respectively
By increasing some characteristics of the study population (such as age, sex, hemoglobin level, white blood cells, blastosis and PPTa) with the presence or not of the risk of DIC occuring, no statistically significant variation was been observed. The same constant was realized by Yanada & al.
The study of hypercoagulability on 40 samples of acute leukaemia demonstrated that there was a risk of disseminated intravascular coagulation in 17.5% of cases according to the criteria of ISTH. Thus, the risk of DIC occurring is indeed present during acute leukaemia. The parameters of haemostasis thus appear to be essential data in the additional assessment during the diagnosis of acute leukaemia.
Nevertheless, understanding the set of pathophysiological mechanisms that support thrombosis formation during acute leukemias would require further exploration by the dosage of FT, factor VII, and some physiological clotting inhibitors such as antithrombin III, C protein and S protein.