P1667: altered coagulation screening tests at diagnosis are a common finding in acute leukemias of both lymphoid and myeloid lineages, and not just in acute promyelocytic leukemia

Background: The acute leukemias (AL) often present with both pro-haemorrhagic and pro-thrombotic complications, through a variety of different mechanisms. Life-threatening consumptive coagulopathy with hyperfibrinolysis is well described in acute promyelocytic leukemias (APL), but non-promyelocytic myeloid leukemias (AML, most notably of monocytic/monoblastic lineage) and lymphoblastic leukemias (ALL) can also develop coagulopathy, often worsened by underproduction thrombocytopenia. Aims: To characterize the presence of altered coagulation screening tests (CST) in (non-APL) AL at diagnosis. Methods: We reviewed all patients (pts) over 18 years old (yo) who presented to our Center with a diagnosis of AL over a 6.5 year period up to 22.02.2022, and who had synchronous diagnostic smears, flow cytometry and CST including fibrinogenemia (Fib) and D-dimers (DD). Fib under 150 mg/dL was considered low (LowFib); DD over 230 ng/mL were considered increased (HiDD). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were analysed as ratios compared to a control (CTR), and were considered increased (>) when over 120%. Results: We studied 188 pts (52% male); 63.3% had AML, 19.7% ALL, 15.4% APL and 1.6% (3 pts) had a biphenotypic AL and were excluded. Ages ranged from 19.2-95.7 yo (mean: 60.3±17.4); AML patients were on average a decade and a half older (65.6±15.3; 51.8±15.3 in APL; 50.9±18.1 in ALL, p<0.001). Within the cohort, 50.5% had a >PT ratio, 11.3% a >aPTT ratio and in 9.7% both were increased; 9.5% of pts had normal Fib and DD, 76.8% had HiDD with normal Fib, and 13.7% had both LowFib and HiDD. Overall, 92.6% of pts had at least one altered test out of four. The mean PT ratio was 1.35±0.75 (1.36±0.31 in APL, 1.39±0.90 in AML, 1.18±0.27 in ALL, p=NS). The proportion of pts with >PT increased from ALL (21.6%) to AML (51.4%) to APL (65.5%), p<0.001. The mean aPTT ratio was 1.00±0.20 (0.94±0.14 in APL, 1.03±0.23 in AML and 0.96±0.13 in ALL, p=0.03); the proportion of pts with >aPTT was not significantly different. ALL pts were twice as likely to have both normal times (80.6%) than AML (39.8%) or APL (34.5%), p=0.001. Mean Fib was lower in APL (178.6±93.4) than AML or ALL (415±199.5 and 351±154.5, p<0.001), with 42.3% of pts with LowFib (7.5% in AML and 0% in ALL, p<0.001). Although the proportion of pts with HiDD was similar in the 3 groups (95.2%, 86.0% and 94.1% in APL, AML and ALL, p=NS), APL pts were more likely to have DD>500 (95.2%, 66.7% and 70.6%, p=0.04), with mean DDs higher in APL (23510±32664) than AML or ALL (3464±6203 and 4399±7248, p<0.001). Overall, 84.7% of pts (including all ALL pts) with HiDD had normal Fib; APL pts were more likely to have both HiDD and LowFib than AML pts (42.9% and 7.0%, respectively, p<0.001). Summary/Conclusion: We found that altered CST were almost universal in AL at diagnosis, irrespective of promyelocytic lineage, with >90% of pts presenting with at least one altered test, most often a prolonged PT – which was found in over half of pts, with its likelihood increasing from one-fifth of pts with ALL to two-thirds of pts with APL, and with ALL pts twice as likely to have normal coagulation times than AML or APL. In concordance with the characteristic coagulopathy of APL, fibrinogenemia in our cohort was 50% lower in APL than in AML or ALL, with almost half of APL pts (but less than 10% of AML pts and no ALL pts) presenting with levels under 150 mg/dL. APL pts were also more likely to have DD over 500 ng/mL (with a mean value that was over five-fold higher than in AML or ALL)¸ and to have both HiDD and LowFib.