He is admitted and started on enoxaparin 1 mg/kg subcutaneously every 12 hours.
By the next morning, he is feeling better and wants to discuss discharge to home and follow-up plans.
Two months ago he presented with abdominal pain and evaluation revealed he had a pancreatic head mass with liver metastases. A liver biopsy was positive for adenocarcinoma consistent with pancreas primary. CA 19-9 level was 1,200 U/mL and he was started on FOLFIRINOX chemotherapy – which he has tolerated well thus far. CA 19-9 and follow-up CT scan show early response to chemotherapy.
Dr. David Henry
Of course, this case raises many questions. Given how successful some directed biomarker-positive therapies are now, you would want to know his microsatellite instability (MSI)/progressive death–ligand 1 (PD-L1) and BRCA mutation status. A high PD-L1 positivity or MSI deficiency would suggest immunoantibody therapy and a BRCA mutation might suggest a poly (ADP-ribose) polymerase inhibitor could play a role.
However, let’s use this case to discuss his venous thromboembolism (VTE) .
Studies show that metastatic cancer patients on chemotherapy might experience a VTE episode of deep vein thrombosis (DVT) or pulmonary embolism (PE) or both as high as 20% of the time during their cancer course and therapy. This patient would be among those who experience the highest incidence of VTE because of the liver metastasis from the pancreatic adenocarcinoma.
So, what to do? Standard treatment of his pulmonary emboli would include either enoxaparin therapeutic dosing 1 mg/kg subcutaneously q12H or 1.5 mg/kg q24H for 3 months. At 3 months, repeat a CT chest scan to show resolution of pulmonary emboli and/or DVT or both, and repeat D-dimer, which should now be well under 1.
But then, there is a second decision to make: Can you stop anticoagulation if his clots have resolved? The answer is yes. If the clots were provoked and the provoking feature is gone you can stop anticoagulation. Patients with pregnancy, on a birth control pill, or on a long trip where immobilization occurred for a extended time (such as driving or flying) can have anticoagulation stopped because the provoking feature is gone, but this is not true in this case. This patient’s pancreas cancer and chemotherapy are ongoing and he will be at increased risk to clot once again if anticoagulation is stopped.
Should this patient have a hypercoagulable workup which might include protein C, protein S, and antithrombin levels? Remember this is quite rare and patients with these deficiencies usually present in their teens or 20s with increased clotting issues. The more common hypercoagulable workup would include checking for factor V Leiden and prothrombin G20210A mutations, as well as acquired antiphospholipid antibodies such as beta2 glycoprotein I, anticardiolipin, and the lupus inhibitor. However, in this 75-year-old cancer patient, these are not necessary or even relevant since his VTE was clearly provoked by metastatic cancer on chemotherapy.
Unfortunately, with metastatic active cancer, anticoagulation would need to be continued at full or possibly half therapeutic dose. Of course, enoxaparin injections can get tiresome for the patient and data suggest the same result can be achieved either with initial management or by continuing anticoagulation management using either rivaroxaban or apixaban.
Wouldn’t it have been better if this patient had never experienced VTE in the first place? Is that possible?
Yes, data suggest that it is. Higher-risk patients like this one could benefit from prophylactic anticoagulation. The Khorana predictive model gives us a simple clinical means to evaluate this and decide who might be at highest VTE risk and who could benefit from low-dose preventive anticoagulation.
In summary, cancer patients undergoing treatment for metastatic disease are at increased risk for symptomatic VTE. Once diagnosed, therapy is usually very effective, but may need to be prolonged as long as the cancer is still active or else, the VTE could recur. Preventive therapy for high-risk patients would be reasonable.
Dr. Henry is a medical oncologist with the Abramson Cancer Center at the University of Pennsylvania, Philadelphia.