Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation

Abstract

History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. Patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset and underwent inverse probability weighting to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Subsequently, multivariable logistic regression model was used to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued it. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p = 0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs discontinued anticoagulation (41% vs 31%, p = 0.08). In a subgroup of 250 allogeneic HCT patients, every one-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower

EHA guidelines on management of antithrombotic treatments in thrombocytopenic patients with cancer

“…17,63,64 For instance, in a well-designed retrospective study, neither proposed platelet transfusion threshold nor platelet count (stratified into platelet count categories using the area under the curve from all platelet counts during follow-up) were predictive of bleeding in patients with anticoagulation and TP postautologous HSCT. 64 Factors associated with bleeding in TP cancer patients are detailed in Table 4, including allogeneic or autologous HSCT, 52 and renal or liver dysfunction. 64 Accordingly, we recommend therapeutic-dose anticoagulation in most patients with grade 1-2 TP who have an indication for anticoagulation post-VTE (Figure 1).…”

“…Several cohort studies have shown that VTE frequently recurs soon after platelet count recovers in patients who do not restart anticoagulation. 52,71 A retrospective study of 250 patients postallogeneic HSCT demonstrated a relative 20% increase in VTE recurrence in patients with prior VTE (most subacute or remote) who did not restart anticoagulation after platelet engraftment, whereas the VTE rates were low during periods of grade 3-4 TP (median 14 d of grade 3-4 TP). 52 Therefore, among patients who have anticoagulation held or reduced during TP, we recommend resuming full-dose anticoagulation as soon as platelet count allows, if the indication persists.…”

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer

“…Several cohort studies have shown that VTE frequently recurs soon after platelet count recovers in patients who do not restart anticoagulation. 52 , 71 A retrospective study of 250 patients postallogeneic HSCT demonstrated a relative 20% increase in VTE recurrence in patients with prior VTE (most subacute or remote) who did not restart anticoagulation after platelet engraftment, whereas the VTE rates were low during periods of grade 3–4 TP (median 14 d of grade 3–4 TP). 52 Therefore, among patients who have anticoagulation held or reduced during TP, we recommend resuming full-dose anticoagulation as soon as platelet count allows, if the indication persists.…”

External validation of the HIGH‐2‐LOW model: A predictive score for venous thromboembolism after allogeneic transplant

“…6 Moreover, for those patients who develop VTE during HCT, the use of anticoagulation therapy is also associated with important rates of clinically significant and fatal bleeding. 1,7 Unfortunately, thrombocytopenia is not a protective factor for the development of VTE, with up to a third of events occurring when the platelet count is less than 50 Â 10 9 /L, and 13% with platelet counts less than 20 Â 10 9 /L. 1 There are no validated VTE risk stratification tools applicable to the HCT population that allow the appropriate selection and timing of pharmacological thromboprophylaxis.…”

“…Patients undergoing HCT, in particular allogeneic, often experience prolonged periods of thrombocytopenia, which predisposes them to a higher risk of clinically relevant hemorrhagic complications 6 . Moreover, for those patients who develop VTE during HCT, the use of anticoagulation therapy is also associated with important rates of clinically significant and fatal bleeding 1,7 . Unfortunately, thrombocytopenia is not a protective factor for the development of VTE, with up to a third of events occurring when the platelet count is less than 50 × 10 9 /L, and 13% with platelet counts less than 20 × 10 9 /L 1 …”