What is the management of anticoagulation in a hospitalized patient with thrombocytopenia (low platelet count) and elevated International Normalized Ratio (INR)?

From the Guidelines

Anticoagulation in admitted CLD thrombocytopenic patients with high INR should be managed with caution, and I recommend using prophylactic doses of low molecular weight heparin (LMWH) such as enoxaparin 40mg subcutaneously once daily, even with platelet counts as low as 50,000/μL and elevated INR values. This approach is supported by the guidance from the SSC of the ISTH, which suggests that full-dose anticoagulation is safe when the platelet count is > 50 × 10^9 L^-1 1. However, for patients with lower platelet counts, a dose-modification strategy using 50% or prophylactic-dose LMWH may be considered 1.

When managing these patients, it is essential to weigh the risks of bleeding against the risks of thrombosis. Despite abnormal coagulation tests, CLD patients often have a rebalanced hemostatic system with both pro- and anticoagulant factors affected, potentially leaving them at risk for thrombosis rather than just bleeding 1. Therefore, monitoring these patients closely with daily complete blood counts and clinical assessment for bleeding is crucial. If therapeutic anticoagulation is required (for conditions like portal vein thrombosis), consider hematology consultation and possibly using anti-Xa levels rather than INR for LMWH monitoring, as INR primarily reflects vitamin K-dependent factors and doesn't accurately represent the overall coagulation status in liver disease 1.

Some key considerations when managing anticoagulation in these patients include:

• Platelet count: avoid anticoagulation only if platelets are below 25,000/μL or if there is active bleeding
• INR values: elevated INR values do not necessarily preclude the use of anticoagulation, but caution is advised
• Type of anticoagulant: LMWH is preferred due to its more predictable pharmacokinetics and lower risk of bleeding compared to unfractionated heparin
• Dose modification: consider reducing the dose of LMWH to 30mg daily or using unfractionated heparin 5000 units subcutaneously twice daily if platelet counts fall below 50,000/μL 1.

Overall, the management of anticoagulation in admitted CLD thrombocytopenic patients with high INR requires a careful and individualized approach, taking into account the patient's specific risk factors and clinical circumstances.

From the FDA Drug Label

Apixaban tablets should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5. 2)] Switching from warfarin to apixaban: Warfarin should be discontinued and apixaban started when the international normalized ratio (INR) is below 2. 0.

The management of anticoagulation in a thrombocytopenic patient with a high INR is not directly addressed in the provided drug label. Thrombocytopenia and high INR are critical factors that require careful consideration when managing anticoagulation.

• The label provides guidance on switching from warfarin to apixaban, recommending that warfarin be discontinued and apixaban started when the INR is below 2.0.
• However, it does not provide specific guidance on managing anticoagulation in thrombocytopenic patients with high INR.
• Given the lack of direct guidance, a conservative approach would be to carefully evaluate the patient's condition and consider consulting with a specialist or following established clinical guidelines for managing anticoagulation in such patients 2.

From the Research

Anticoagulation in Admitted Thrombocytopenic Patients with High INR

• The management of thrombocytopenic patients with high International Normalized Ratio (INR) values poses a significant challenge due to the increased risk of bleeding complications 3.
• A study published in 2017 found that warfarinized thrombocytopenic patients are at a higher risk of minor bleeding complications, with a higher tendency for major bleeding, but derive similar benefits against thrombotic events compared to patients with normal platelet counts 3.
• The same study suggested that a narrow INR target with an upper limit below 2.5, together with closer anticoagulation monitoring, may improve the safety of patients 3.

Use of Direct Oral Anticoagulants (DOACs) in Thrombocytopenic Patients

• Direct Oral Anticoagulants (DOACs) such as rivaroxaban and apixaban have been used in the treatment of suspected or confirmed heparin-induced thrombocytopenia (HIT) 4.
• A retrospective chart review published in 2022 found that DOACs are being increasingly utilized for the treatment of confirmed or suspected HIT, with no new thrombosis reported during hospitalization 4.
• However, there have been reports of rivaroxaban-induced thrombocytopenia, highlighting the need for careful monitoring of platelet counts in patients receiving DOACs 5.

Platelet Cut-off for Anticoagulant Therapy in Thrombocytopenic Patients

• An expert consensus published in 2019 recommended a platelet cut-off for safe administration of low molecular weight heparin (LMWH) in thrombocytopenic patients with blood cancer and venous thromboembolism (VTE) 6.
• The consensus suggested that anticoagulation with LMWH at therapeutic doses is safe for platelet counts between ≥50<100×10^9/L, and at 50% dose reduction for platelet counts ≥30<50×10^9/L 6.

Management of High INR Values

• A study published in 2012 found that an INR higher than 9 is associated with a high risk of bleeding, and that withholding warfarin or giving vitamin K treatment may be ineffective at reducing the INR within 24 hours 7.
• The study suggested that plasma infusion may be needed to reduce INR and the risk of bleeding within 24 hours, particularly in hospitalized patients with underlying disease, comorbidities, and medications 7.