Disseminated intravascular coagulation scores predict venous, arterial thrombosis risk in AML

Approximately 10% of newly diagnosed patients with acute myeloid leukemia will develop venous and arterial thrombosis after treatment with intensive chemotherapy, according to prospective study results published in Blood.

Disseminated intravascular coagulation at the time of diagnosis served as a strong predictor of potential thrombotic events, results showed.

“Venous thromboembolism is a common complication in patients with cancer,” Frank W.G. Leebeek, MD, PhD, professor of hematology at Erasmus University Medical Center in Rotterdam, Netherlands, and colleagues wrote. “Among patients with hematological malignancies, those with acute lymphoid leukemia and multiple myeloma are particularly prone to develop VTE, with incidences of 6% during induction chemotherapy and 10% to 28% during induction chemotherapy, respectively.”

Recent studies have shown that patients with hematologic malignancies may be at an increased risk for arterial thrombotic events (ATE), especially within the first months following diagnosis.

Limited data exist as to whether patients with AML have an increased risk for VTE or ATE. Leebeek and colleagues sought to study the incidence of these complications in a cohort of newly diagnosed patients. The study included data from 276 adult patients (mean age, 47 years; range, 18-65) treated at Erasmus University Medical Center between 2001 and 2010, as well as a validation cohort comprised of 135 patients aged older than 60 years (mean age, 68 years; range, 61-77).

The researchers assessed markers of disseminated intravascular coagulation — including fibrinogen, D-dimer levels, alpha-2-antiplasmin, antithrombin, prothrombin time and platelet counts — and the associations they had on the incidence of VTE and ATE during follow-up.

No patients on the study received anticoagulant prophylaxis. The researchers used compression ultrasonography, CT scans or both to confirm diagnoses in patients suspected of having thrombotic events.

Median follow-up was 478 days (range, 0-109 months).

The younger cohort had a thrombosis prevalence of 8.7% (VTE, 4.7%; ATE, 4%), including pulmonary embolism (2.9%), venous thrombosis of the leg (1.4%) and thrombosis of the upper extremity (0.4%). Arterial events included myocardial infarction or acute coronary event (1.4%), ischemic stroke (1.4%), transient ischemic attack (0.4%) and other arterial thrombotic events (0.7%).

Two patients developed arterial events after the occurrence of a venous thrombotic event.

Eighteen patients developed a symptomatic venous thrombosis (n = 9) or arterial thrombotic event (n = 9). One patient had a thrombotic event 4 days prior to the start of chemotherapy, with 12 patients developing thrombosis after initiating chemotherapy but prior to the second course (median time from initiation, 8 days; range, 2-60).

Five patients had an event after starting the second chemotherapy course (median, 32 days; range, 6-47). Two patients experienced a fatal cerebral vascular incident.

The validation cohort had a thrombosis prevalence of 10.4% (VTE, 4.4%; ATE, 5.9%), including PE (1.5%), venous thrombosis of the leg (2.2%) and thrombosis of the upper extremity (0.7%).

MI occurred in 2.2% of these patients, ischemic stroke in 2.9% and peripheral artery disease in 0.7%.

Disseminated intravascular coagulation scores ( 5) appeared significantly predictive of VTE and ATE (HR = 4.79; 95% CI, 1.71-13.45), a finding validated in the confirmation cohort (HR = 11.08; 95% CI, 3.23-38.06).

D-dimer levels served as the most predictive marker for thrombosis in the younger cohort (HR = 12.3; 95% CI, 3.39-42.64) and the validation cohort (HR = 7.82; 95% CI, 1.95-31.38).

The researchers identified their inability to collect data on acquired and inherited thrombophilic factors as a study limitation. They further noted that 22 patients in the initial cohort had used anticoagulants for prior thrombosis.

“Our study clearly revealed that we were able to identify [patients with AML] at high risk for thrombosis by measuring disseminated intravascular coagulation parameters at diagnosis of AML,” Leebeek and colleagues wrote. “It seems, therefore, of potential clinical interest to perform prospective studies to evaluate the potential role of prophylactic anticoagulation therapy in patients at high risk of thrombosis, especially during the first month after start of treatment.” – by Cameron Kelsall

Disclosure: One study researcher reports a consultant role with Johnson & Johnson. Leebeek and the other researchers report no relevant financial disclosures.