Patients with a hematologic malignancy who are receiving curative-intent chemotherapy or hematopoietic cell transplantation (HCT) have an increased risk of venous thromboembolism (VTE), despite commonly experiencing prolonged periods of thrombocytopenia. The management of thrombosis in this patient setting is difficult, but research presented at the 2016 ASH Annual Meeting suggests that patients with low platelet counts receiving anticoagulation to minimize VTE risk are not at an increased risk for major bleeding.
Bethany T. Samuelson, MD, from the Department of Medicine at the University of Washington in Seattle, Washington, and colleagues from the Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center performed a retrospective chart review of cases of VTE diagnosed between January 1, 2009, and December 31, 2014, to determine if patients who require anticoagulation could prevent thrombosis without increasing the risk of bleeding, and whether these patients could safely receive platelet transfusion above the ≥50 x 109 threshold.
The investigators identified 79 adult patients receiving chemotherapy for acute leukemia or HCT for a hematologic malignancy who experienced a ≥5-day period of moderate to severe treatment-related thrombocytopenia (platelets <50 x 109) within 30 days of VTE diagnosis at the three participating centers. Patients were excluded if records were not available for a portion of this thrombocytopenic period. Charts were reviewed for diagnostic and treatment information, including management of anticoagulation, use of platelet transfusions, and bleeding and thrombotic events.
Eighty-three events occurred among the 79 patients identified, including:
- 64 catheter-associated thromboses (CAT)
- 11 lower-extremity deep-vein thromboses
- 8 pulmonary embolisms (PEs)
Sixty-six patients (80%) were started on anticoagulation at the time of diagnosis.
Thirty-six patients did not experience bleeding, while 23 experienced World Health Organization (WHO) grade 2 bleeding events, and 10 experienced WHO grade 3/4 bleeding events (TABLE). Mean and median platelet counts at the time of a bleeding event were lower among patients who experienced a mild (grade 2) bleeding event than for patients who experienced a moderate or severe (grade 3/4) bleeding event.
“While patients who experienced a platelet count below the 50 x 109 goal for five days or longer had higher rates of minor (Grade 2) bleeding, increased rates of clinically significant (grade 3/4 bleeding) were not observed,” Dr. Samuelson noted.
The length of thrombocytopenic episodes also appeared to be associated with a greater risk of mild bleeding events (mean duration of thrombocytopenia = 11.5 days; p=0.015), but not moderate or severe bleeding events (mean duration of thrombocytopenia = 5.0 days; p=0.034), even among patients who were receiving anticoagulation.
The platelet transfusion threshold was set at ≥50 x 109 for the majority of anticoagulated patients (n=61; 92%), which Dr. Samuelson said was common “in the absence of evidence to guide anticoagulation and thrombosis risk management” in this setting. However, “patients experienced a number of negative effects potentially related to transfusions”, including eight patients who experienced transfusion reactions (7 cases of hives and 1 febrile non-hemolytic transfusion reaction), and 25 who experienced volume overload that may have been associated with or worsened by platelet transfusions. Ten patients discontinued anticoagulation because the platelet count could not be maintained above the 50 x 109 threshold; four of these patients experienced progression of thrombosis and one patient with CAT developed a possible/probable PE.
The optimal platelet transfusion threshold for patients who require anticoagulation, therefore, should be the subject of future investigations, the authors concluded.
Samuelson BT, Walter RB, Gernsheimer T, et al. A Platelet count <50 x 109 was not associated with increased rates of major bleeding among anticoagulated patients. Abstract #164. Presented at the 2016 ASH Annual Meeting, December 3, 2016; San Diego, California.
|TABLE. Outcomes Related to Bleeding Events|
|WHO Grade 2
|WHO Grade 3/4
|Mean platelet count||91||81||98||0.547*
|Median mean platelet count||76||60||74||−|
|Mean platelet count at time of bleed||−||85||159||0.23|
|Median platelet count at time of bleed||−||55||70||−|
|Mean days on anticoagulation||21.2||22.6||18.7||0.340*
|Mean days <50 x 109||6.7||11.5||5||0.192*
|Median days <50 x 109||5||8||4||−|
|Percentage of days on anticoagulation with platelets <50 x 109||24.8||56.5||35.9||0.975*
|Percentage of events occurring at <50 x 109||−||40%||20%||−|
|*Grade 3/4 bleeding vs. not
**No bleeding vs. grade 2 bleeding
***Grade 2 vs. grade 3/4 bleeding
WHO = World Health Organization