Management of Coagulopathy in Myelofibrosis
Coagulopathy in myelofibrosis requires risk-stratified management focused on preventing thrombosis in high-risk patients while carefully monitoring for bleeding complications, particularly in those with thrombocytopenia or on anticoagulation. 1, 2
Initial Assessment and Risk Stratification
Before initiating any treatment, evaluate for coagulopathy through:
- Coagulation testing to assess for acquired von Willebrand disease (VWD) and other coagulopathies, particularly in patients undergoing high-risk surgical procedures, those with elevated platelet counts, splenomegaly, or unexplained bleeding 1
- Complete evaluation including age, thrombosis history, JAK2 mutation status, and IPSS risk category, as these are independent predictors of thrombotic risk 2
- Assessment of platelet count extremes: thrombocytosis >1,500 × 10⁹/L increases bleeding risk through acquired VWD, while thrombocytopenia increases hemorrhagic complications 1, 3
Thrombosis Prevention and Management
High-Risk Patients (Age >60 years, prior thrombosis, or JAK2 mutation)
Initiate low-dose aspirin (81-100 mg daily) for all patients without contraindications to reduce thrombotic risk 1. However, aspirin should be used with extreme caution in patients with acquired VWD 1.
For patients with active thrombosis, use clinically appropriate anticoagulation (low-molecular-weight heparin, direct oral anticoagulants, or warfarin) based on current ACCP Guidelines 1. The duration depends on:
- Severity of thrombotic event (abdominal vein thrombosis requires longer duration than DVT)
- Degree of disease control
- Assessment of recurrence likelihood 1
Cytoreductive therapy should be initiated or intensified to control myeloproliferation and reduce thrombotic risk 1:
- Hydroxyurea is first-line for older patients 1
- Interferons are preferred for younger patients or those of childbearing age 1
Special Thrombotic Considerations
Patients on immunomodulatory agents face increased venous thrombosis risk and require heightened surveillance 2. JAK2-mutated patients with prior thrombosis represent the highest-risk subgroup for early thrombotic events 2.
Bleeding Management
Assessment and Initial Management
Rule out and treat coexisting causes of bleeding before attributing hemorrhage solely to myelofibrosis 1.
Withhold aspirin immediately until bleeding is controlled, then reassess risk-benefit ratio 1.
Normalize platelet counts using appropriate cytoreductive therapy in patients with extreme thrombocytosis and bleeding 1.
High-Risk Bleeding Scenarios
Patients in intermediate-2/high-risk IPSS categories on anticoagulation have nearly sevenfold increased major bleeding risk 2. For these patients:
- Consider dose reduction or temporary discontinuation of anticoagulation
- Maintain platelet counts >30-50 × 10⁹/L if possible 4
- Monitor closely for gastrointestinal bleeding, especially with splenomegaly and portal hypertension 1
For gastrointestinal bleeding with splenomegaly, obtain urgent consultation with hepatology or gastroenterology for endoscopic evaluation of potential gastric varices 1.
Plateletpheresis Indication
Plateletpheresis may be indicated in essential thrombocythemia patients with acute life-threatening thrombosis or severe bleeding, though this is less commonly applicable to primary myelofibrosis 1.
Perioperative Management
Multidisciplinary coordination with surgical teams is essential, including:
- Review of bleeding and thrombosis history
- Medication reconciliation 1
Emergency surgery should proceed as necessary with close postoperative surveillance for arterial/venous thrombosis and bleeding 1.
Coagulation testing for acquired VWD is mandatory before high-risk surgical procedures in patients with elevated platelet counts, splenomegaly, or unexplained bleeding 1.
Monitoring and Follow-up
Regular assessment every 3-6 months should include:
- Complete blood counts to monitor platelet trends 1
- Evaluation for new thrombotic or bleeding events 1
- Assessment of splenomegaly progression 1
The overall incidence of thrombosis in myelofibrosis is 1.65 per 100 patient-years, with major bleeding at 1.5 per 100 patient-years 2, emphasizing the need for vigilant monitoring of both complications.
Critical Pitfalls to Avoid
Do not assume cytoreductive or anti-thrombotic therapy eliminates thrombotic risk—no decreased incidence of thrombosis was observed in treated patients in registry data 2.
Avoid routine anticoagulation in intermediate-2/high-risk patients without clear indication, given the sevenfold increased bleeding risk 2.
Do not overlook acquired VWD in patients with extreme thrombocytosis (>1,500 × 10⁹/L), as this paradoxically increases bleeding risk despite high platelet counts 1.