How do you manage MPN patients with acquired VWD in the perioperative setting?

The greatest risk of a very high platelet is bleeding not thrombosis, and it is fair to say that this appears to apply to myeloproliferative (MPN) thrombocytosis as opposed to reactive thrombocytosis (there is no correlation between the platelet count and thrombosis with either cause of thrombocytosis).This may be a consequence of the differences in platelet size (MPV) between the two forms of thrombocytosis, since bleeding is usually due to a loss of the most hemostatically-active forms of von Willebrand factor, the high molecular weight multimers, which are adsorbed and destroyed by the platelets. This consequence, known as acquired von Willebrand syndrome (AVWS) is platelet count-dependent, and most commonly observed when the platelet is ≥ 1,500,000/mL. However, I have encountered AVWS in a polycythemia vera patient with a platelet count of 900,000/mL. This is not to suggest that MPN patients should be routinely screened for AVWS, since bleeding is rarely, if ever, spontaneous, particularly when the platelet count is < 1,500,000/mL. 

The ristocetin cofactor assay (RCA) is a simple way to screen for AVWS. Values below 50% are abnormal, but not an indication for therapy in the absence of bleeding. A caveat about the assay is that prolonged storage of the blood sample could result in an abnormal result; the blood should be assayed as soon as possible. Checking for AVWS would apply to MPN patients who require aspirin therapy for a medical indication or before invasive surgery; prophylactic aspirin, without a medical indication, is never indicated for MPN thrombocytosis since it does not prevent thrombosis or cardiovascular disease either; in patients over age 60, it could provoke bleeding. 

Dental and superficial plastic surgery procedures can usually be covered with an oral antifibrinolytic agent (I prefer oral tranexamic acid over Amicar because of ease of dosing) without lowering the platelet count, starting the morning of surgery and continuing for several days after. For invasive surgery, platelet count reduction is the best practice for preventing AVWS because it is the most direct, and antifibrinolytics are prothrombotic. Hydroxyurea (HU) is an easy way to lower the platelet count if used correctly. By this I mean, don’t let perfect be the enemy of the good. You do not need to take the platelet count below 600,000/mL before stopping the HU and you can monitor your progress with an RCA. Remember, when you stop HU, its effect continues and you will see the platelet count continue to fall; if you stop HU at a platelet count of 150,000/mL, you will end up with a platelet count of 2000/mL and a guaranteed rebound thrombocytosis. In an emergency, don’t depend on plateletpheresis; it is inefficient even at a platelet count of 2,500,000/mL. I would choose Humate-P because it has both VW Factor and Factor VIII but there is little information about this in the MPN.