Aspirin
–
Primary prevention
Stop
Secondary prevention
Stop during conditioning, resume when platelets > 50,000
Coronary stent
–
Bare metal
Combined therapy (ASA = aspirin + P2Y12 Inhibitor) 4 weeks, then ASA thereafter. Continue ASA until platelet count < 20,000, then resume when > 20,000
Drug eluting
If possible, delay transplant until 1 year after stent placement. If unable, combined therapy throughout transplant. After 1 year, continue ASA until platelet count < 20,000 then resuming when > 20,000
Atrial fibrillation
–
CHADS2 0–2
Stop ASA during conditioning, resume when platelets > 50,000
CHADS2 > 2
Therapeutic LMWH until platelets < 50,000, prophylactic dosing when platelets 20–50,000
Mechanical heart valve
Therapeutic LMWH until platelets < 50,000, prophylactic doses 20–50,000
Acute events
–
Catheter thrombosis
Remove catheter, consider anticoagulation if symptomatic and platelets > 50,000
Distal thrombosis
Follow-up scans in 3 days, then weekly
Proximal thrombosis and PE
Therapeutic LMWH if platelets > 50,000, prophylactic doses 20–50,000, IVC filter if platelets < 20,000
Acute coronary syndrome
ASA for all patients regardless of platelet count
–
Individual therapy for patient per cardiology recommendations
a.
Primary prevention:
i.
A significant portion of the population is on aspirin or other antiplatelet agents.
ii.
In recent years, the use of these drugs for primary prevention of first myocardial infarction (MI) or cerebrovascular accident (CVA) has been become controversial.
iii.
The absolute reduction in events is very small and almost balanced by the increase risk in bleeding. Therefore, for a hematopoietic stem cell transplantation (HSCT) recipient taking antiplatelet agents for primary prevention, the most reasonable strategy would be to stop the medication.
b.
Secondary prevention:
i.
The benefits of antiplatelet therapy in patients who have suffered a MI or CVA are more robust with patients seeing a 22 % reduction in vascular events.
ii.
A reasonable strategy would be to stop the drug when conditioning starts and then resume when platelets have recovered to > 50,000/ul.
iii.
Patients with a history of MI, CVA, or vascular disease but not previously on therapy should be started on aspirin 81 mg po daily (or clopidogrel 75 mg po daily if aspirin intolerant) when platelets have recovered to > 50,000/ul.
c.
Patients with coronary stents:
i.
Management of patients with coronary stents is difficult because stopping antiplatelet therapy is strongly associated with stent thrombosis. This can be fatal in up to 50 % of patients.
ii.
The risk is most extreme for bare metal stents for 4 weeks after placement and with first generation drug-eluting stents (DES) up to 1 year after placement. During this period, even stopping just clopidogrel is associated with adverse outcomes.
iii.
For a patient with a DES who requires HSCT during the “at-risk” period, it may be prudent to continue dual antiplatelet therapy throughout the phase of thrombocytopenia unless bleeding develops.
iv.
If possible, consideration should be given to delaying transplant until 1 year after DES placement. Consultation with cardiology is mandatory to determine safe timing for HSCT.
v.
For patients with stents outside the high-risk period, continuing aspirin until the platelet count is < 20,000/ul, then resuming when > 20,000/ul can be considered.
13.2 Antithrombotic Therapy
1.
Choice of therapy during HSCT:
a.
Although warfarin (Coumadin®) is the antithrombotic agent of choice for most patients, many of its properties make it undesirable for the HSCT patient:
i.
Warfarin requires close monitoring, has many drug–drug and food interactions, and its half-life is 36 h making it impractical to quickly start and stop if necessitated by changes in clinical condition.
ii.
Measurements of anticoagulation are influenced by vitamin K intake.
b.
The most practical antithrombotic agents for use during HSCT are the low molecular weight heparins (LMWH) . The lack of interactions and the relatively short half-life (~ 4 h) simplifies their use in this setting. All of these agents are renally cleared so close monitoring is required (Table 13.2).
Table 13.2
Low molecular weight heparins
Drug | Prophylactic dosing | Therapeutic dosing | Pediatric dosinga |
|---|---|---|---|
Dalteparin | 2500 units/day | 100 units/kg q 12 h | – |
Enoxaparin | 40 mg/day | 1 mg/kg q 12 h or 1.5 mg/kg/day in low risk patients | < 5 kg: 1.5 mg/kg q 12 h > 5 kg: 1 mg/kg q 12 h |
Tinzaparin | 3500 units/day | 175 units/day | – |
c.
There are no clear guidelines for anticoagulation in the setting of thrombocytopenia; however, most experts would recommend no full-dose anticoagulation below a platelet count of 50,000/ul and no prophylactic anticoagulation below a platelet count of 20,000/ul.
d.
In theory, one can transfuse platelets to try to maintain the platelet count above these thresholds; however, in practice this is difficult and associated with excess bleeding.
2.
Atrial fibrillation:
a.
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The leading indication for warfarin in older patients is CVA prevention from atrial fibrillation.
i.
It is estimated that 15 % of all CVAs can be attributed to atrial fibrillation. Warfarin has reduced the CVA rate from 5 % per year to 1 %.
ii.
While warfarin benefits most patients, those who previously have had CVAs are at a higher risk of recurrent CVA and appear to benefit the most from anticoagulation.
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