Initial management strategies in a patient with a catastrophic thrombotic presentation
| Initial intervention . | Initial results . | Subsequent management . |
|---|---|---|
| Normal PT, aPTT, and platelet count | ||
| Start UFH | • Target aPTT achieved | • Follow aPTT, platelet counts, and clinical course |
| • Unable to achieve target aPTT (ie, subtherapeutic results) | • Check anti–factor Xa level (confirm heparin present) | |
| • Check factor VIII and fibrinogen levels (evaluate for acute-phase response) | ||
| • Check antithrombin level (evaluate for acquired deficiency) and consider supplementation if low | ||
| • Continue to escalate UFH dose or consider an alternative anticoagulant (e.g., LMWH, argatroban, bivalirudin) | ||
| • Development of thrombocytopenia | • Recheck PT, fibrinogen, and D-dimer (evaluate for DIC) | |
| • Reevaluate blood film (evaluate for MAHA) | ||
| • Check anti-PF4/heparin immunoassay (evaluate for HIT) | ||
| • Consider changing from UFH to an alternative anticoagulant if HIT is strongly suspected | ||
| • New thrombotic event (“anticoagulant failure”) | • Recheck aPTT, anti–factor Xa level (assess drug effect) | |
| • Consider alternative treatment strategies (eg, alternative anticoagulant, thrombolytic therapy, initiation of plasma exchange or immunomodulatory therapy) | ||
| Normal PT and platelet count, prolonged aPTT | ||
| Obtain/review additional laboratory tests, including baseline and serial fibrinogen and D-dimer levels | • Results consistent with, or suggestive of, a LA | • Obtain ELISA testing for aPL (aCL, aβ2GPI) |
| • Start UFH, use anti–factor Xa levels adjust heparin dose; alternatively, if renal function is normal and an operation or invasive procedure is unlikely, therapeutic LMWH or fondaparinux could be used | ||
| • Results suggestive of factor deficiency or possible consumptive state | • Assess hemorrhagic risk and safety of anticoagulant therapy | |
| • If hemorrhagic risk is excessive,* or active bleeding, consider mechanical interventions (e.g., IVC filter, thrombectomy) | ||
| • Frequent reevaluation and initiation of anticoagulant therapy as soon as hemorrhagic risk is not excessive | ||
| Normal PT and aPTT, low platelet count (eg, <100 × 109/L) | ||
| Obtain/review additional laboratory tests, including baseline and serial fibrinogen and D-dimer levels | • Results consistent with MAHA | • Obtain/review laboratory testing for aPL (LA, aCL, aβ2GPI) and ADAMTS13 |
| • If TTP is suspected, consider initiation of plasma exchange, corticosteroids, rituximab | ||
| • If catastrophic APS is suspected, initiate anticoagulant therapy with UFH and corticosteroids, +/− plasma exchange and/or IVIG | ||
| • Isolated thrombocytopenia, no other abnormalities noted | • If low platelet count is new (i.e., prior platelet counts normal) and confirmed by repeat testing, consider sending testing for anti-PF4/heparin antibodies and initiating anticoagulant therapy with argatroban or bivalirudin if HIT is strongly suspected | |
| Prolonged PT and/or aPTT, low platelet count (eg, <100 × 109/L) | ||
| Obtain/review additional laboratory tests, including baseline and serial fibrinogen and D-dimer levels | • Results consistent with DIC | • Assess hemorrhagic risk to determine whether anticoagulant therapy can be safely administered or alternative strategies need to be considered |
| • Frequent follow-up of laboratory testing to assess progress | ||
| • Initiate anticoagulant therapy with UFH as soon as hemorrhagic risk is acceptable, and monitor with anti-factor Xa levels if aPTT is abnormal |
| Initial intervention . | Initial results . | Subsequent management . |
|---|---|---|
| Normal PT, aPTT, and platelet count | ||
| Start UFH | • Target aPTT achieved | • Follow aPTT, platelet counts, and clinical course |
| • Unable to achieve target aPTT (ie, subtherapeutic results) | • Check anti–factor Xa level (confirm heparin present) | |
| • Check factor VIII and fibrinogen levels (evaluate for acute-phase response) | ||
| • Check antithrombin level (evaluate for acquired deficiency) and consider supplementation if low | ||
| • Continue to escalate UFH dose or consider an alternative anticoagulant (e.g., LMWH, argatroban, bivalirudin) | ||
| • Development of thrombocytopenia | • Recheck PT, fibrinogen, and D-dimer (evaluate for DIC) | |
| • Reevaluate blood film (evaluate for MAHA) | ||
| • Check anti-PF4/heparin immunoassay (evaluate for HIT) | ||
| • Consider changing from UFH to an alternative anticoagulant if HIT is strongly suspected | ||
| • New thrombotic event (“anticoagulant failure”) | • Recheck aPTT, anti–factor Xa level (assess drug effect) | |
| • Consider alternative treatment strategies (eg, alternative anticoagulant, thrombolytic therapy, initiation of plasma exchange or immunomodulatory therapy) | ||
| Normal PT and platelet count, prolonged aPTT | ||
| Obtain/review additional laboratory tests, including baseline and serial fibrinogen and D-dimer levels | • Results consistent with, or suggestive of, a LA | • Obtain ELISA testing for aPL (aCL, aβ2GPI) |
| • Start UFH, use anti–factor Xa levels adjust heparin dose; alternatively, if renal function is normal and an operation or invasive procedure is unlikely, therapeutic LMWH or fondaparinux could be used | ||
| • Results suggestive of factor deficiency or possible consumptive state | • Assess hemorrhagic risk and safety of anticoagulant therapy | |
| • If hemorrhagic risk is excessive,* or active bleeding, consider mechanical interventions (e.g., IVC filter, thrombectomy) | ||
| • Frequent reevaluation and initiation of anticoagulant therapy as soon as hemorrhagic risk is not excessive | ||
| Normal PT and aPTT, low platelet count (eg, <100 × 109/L) | ||
| Obtain/review additional laboratory tests, including baseline and serial fibrinogen and D-dimer levels | • Results consistent with MAHA | • Obtain/review laboratory testing for aPL (LA, aCL, aβ2GPI) and ADAMTS13 |
| • If TTP is suspected, consider initiation of plasma exchange, corticosteroids, rituximab | ||
| • If catastrophic APS is suspected, initiate anticoagulant therapy with UFH and corticosteroids, +/− plasma exchange and/or IVIG | ||
| • Isolated thrombocytopenia, no other abnormalities noted | • If low platelet count is new (i.e., prior platelet counts normal) and confirmed by repeat testing, consider sending testing for anti-PF4/heparin antibodies and initiating anticoagulant therapy with argatroban or bivalirudin if HIT is strongly suspected | |
| Prolonged PT and/or aPTT, low platelet count (eg, <100 × 109/L) | ||
| Obtain/review additional laboratory tests, including baseline and serial fibrinogen and D-dimer levels | • Results consistent with DIC | • Assess hemorrhagic risk to determine whether anticoagulant therapy can be safely administered or alternative strategies need to be considered |
| • Frequent follow-up of laboratory testing to assess progress | ||
| • Initiate anticoagulant therapy with UFH as soon as hemorrhagic risk is acceptable, and monitor with anti-factor Xa levels if aPTT is abnormal |
Initial laboratory data obtained in the absence of any anticoagulant therapy.
aβ2GPI, anti-β-2-glycoprotein I antibody; aCL, anti-cardiolipin antibody; LA, lupus anticoagulant; MAHA, microangiopathic hemolytic anemia; UFH, unfractionated heparin.
The hemorrhagic risk for an individual patient needs to be determined based on clinical criteria, including recent procedures, trauma, or evidence for bleeding, and laboratory parameters, including the platelet count, fibrinogen level, etc. For the patient described in the text, the presence of DIC, severe thrombocytopenia, and extensive dural sinus thrombosis was felt to represent an excessive hemorrhagic risk and hindered initial attempts at anticoagulant therapy.