What venous thromboembolism (VTE) prophylaxis to use in a patient with cirrhosis and thrombocytopenia (low platelets) during hospital stay?

From the Guidelines

For a 48-year-old man with cirrhosis and low platelets (thrombocytopenia), INR 1.3, low-dose enoxaparin (40 mg subcutaneously once daily) or unfractionated heparin (5,000 units subcutaneously every 8-12 hours) is generally recommended for VTE prophylaxis during hospitalization, even with platelet counts as low as 50,000/μL, as suggested by the most recent guidelines 1.

Key Considerations

• The decision for VTE prophylaxis should be individualized based on the patient's bleeding risk versus thrombotic risk.
• Despite low platelet counts, patients with cirrhosis often have rebalanced hemostasis and may actually be prothrombotic due to decreased production of anticoagulant factors and increased levels of procoagulant factors like Factor VIII and von Willebrand factor.
• Regular monitoring of platelet counts, anti-Xa levels (if using LMWH), and signs of bleeding is essential.
• For patients with active bleeding or at very high bleeding risk, mechanical prophylaxis alone may be the safest option until the bleeding risk decreases.

Specific Recommendations

• For severe thrombocytopenia (platelets <50,000/μL), consider reducing the dose of enoxaparin to 20 mg daily or using mechanical prophylaxis with intermittent pneumatic compression devices if pharmacological prophylaxis is contraindicated.
• The use of prophylactic anticoagulation in hospitalized patients with cirrhosis may reduce the risk of symptomatic deep venous thrombosis, but the evidence is based on studies in the general medical population due to the lack of specific RCTs in patients with cirrhosis 1.

Guideline Evidence

• The AGA clinical practice guideline suggests standard anticoagulation prophylaxis over no anticoagulation in hospitalized patients with cirrhosis who otherwise meet standard guidelines for the use of VTE prophylaxis, despite the very low certainty of evidence 1.
• The EASL clinical practice guidelines provide insights into the use of LMWH and UFH in patients with cirrhosis, highlighting the need for individualized decisions based on bleeding and thrombotic risks 1.

From the FDA Drug Label

The most widely used dosage has been 5,000 units 2 hours before surgery and 5,000 units every 8 to 12 hours thereafter for 7 days or until the patient is fully ambulatory, whichever is longer. For patients with cirrhosis and thrombocytopenia, no specific dosage is recommended, but it is essential to monitor platelet counts, hematocrit, and occult blood in stool during the entire course of heparin therapy.

Venous Thromboembolism (VTE) Prophylaxis:

• The patient can be given low-dose heparin as VTE prophylaxis, with a dose of 5,000 units every 8 to 12 hours, subcutaneously.
• It is crucial to monitor platelet counts and adjust the dose according to the patient's condition and laboratory results.
• Close monitoring of the patient's coagulation status, including INR and aPTT, is necessary to minimize the risk of bleeding complications.
• The use of heparin in patients with cirrhosis and thrombocytopenia should be done with caution, and the patient should be closely monitored for signs of bleeding or thrombocytopenia 2.

From the Research

Venous Thromboembolism (VTE) Prophylaxis in Patients with Cirrhosis and Thrombocytopenia

• The patient in question has cirrhosis, low platelets, and an INR of 1.3, which may pose a challenge in deciding the appropriate VTE prophylaxis during hospital stay.
• According to 3, mild to moderate thrombocytopenia (> 50,000/μL) should not interfere with VTE prevention decisions, but severe thrombocytopenia (< 50,000/μL) requires individual consideration.
• A study by 4 found that the use of VTE chemoprophylaxis with enoxaparin was suboptimal in cirrhotic patients, with platelet count and INR being independent predictors of prophylaxis use.
• Guidance from the SSC of the ISTH 5 recommends against using thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis in hospitalized patients with cirrhosis.
• The same guidance suggests anticoagulant thromboprophylaxis in line with local protocols, with low molecular weight heparin (LMWH) or fondaparinux preferred over unfractionated heparin (UFH).
• A study by 6 found that cirrhotic patients were less likely to receive pharmacologic prophylaxis, but the incidence of VTE did not statistically differ from that in noncirrhotic patients.
• Another study by 7 discussed the possibilities and caveats of using established and new-generation antithrombotic drugs in patients with cirrhosis, highlighting the need for careful consideration of the benefits and risks of antithrombotic treatment in this population.

Recommendations for VTE Prophylaxis

• Based on the available evidence, it is recommended to consider anticoagulant thromboprophylaxis in patients with cirrhosis and thrombocytopenia, taking into account the individual patient's risk-benefit ratio.
• LMWH or fondaparinux may be preferred over UFH, and the decision to use pharmacologic prophylaxis should be made in accordance with local protocols and guidelines.
• The patient's platelet count and INR should not be used as absolute contraindications to anticoagulant thromboprophylaxis, but rather as factors to consider in the overall assessment of the patient's risk of VTE and bleeding.