Question: Dr. Chiragbhai, thank you for explaining in last part about Polycythemia vera – including risk of thrombosis, JAK 2 mutation for diagnosis, good prognosis with treatment, and phlebotomy as the main treatment. Most patients can be treated without medicine use is really interesting fact.
Ans: One more important fact about polycythemia vera is regarding perioperative management. These patients are at high risk of thrombosis after surgery if not managed well. Hematocrit should be brought in normal range for several weeks before any elective surgery.
Also, during pregnancy they have a high risk of thrombosis. Hematocrit should be controlled well throughout pregnancy, preferably less than 37%. Hydroxyurea is contraindicated. Interferon alpha should be used during pregnancy. Low dose iron can be given during pregnancy.
Also, chlorambucil and busulfan which were old standards are not preferred due to high risk of AML/MDS with long term use.
Que: Can you tell us something about next myeloproliferative neoplasm ET – Essential Thrombocytosis?
Ans: ET is also a very interesting disorder, with probably best prognosis among all MPNs. Almost 50% patients are diagnosed incidentally without any symptoms. Rest of the patients have either vasomotor symptoms or thrombosis or hemorrhage as presenting symptom. Vasomotor symptoms are largely nonspecific, such as headache, visual disturbances, dizziness, burning dysesthesia of palms and soles (erythromelalgia), acrocyanosis, cognitive or psychiatric deficits, etc. Diagnosis requires exclusion of reactive thrombocytosis, other MPNs, MDS. There is no one test or platelet count which is diagnostic for ET. Platelet count of even more than 20 lac (2,000,000) is possible in reactive causes. Commonest reactive causes include Iron deficiency, Infection, Inflammation. Also important are various cancers, lack of splenic function, acute blood loss, and others. CRP, ferritin, ESR may help in ruling out occult infection/inflammation.
Even with normal wbc count, it is important to rule out CML by use of PCR for BCR-ABL.
JAK 2 mutation is helpful in diagnosis, but is absent in about 30% cases. Diagnosis also requires sustained platelet count over 450,000, and bone marrow showing megakaryocytic hyperplasia.
Que: You mentioned about hemorrhage as one symptom. How is that possible with a high platelet count?
Ans: Yes, that is a good question. With platelet counts over 1,000,000 there is a higher risk of bleeding, primarily because of too many platelets adsorbing von willebrand factor, an essential component of clotting mechanism. Hence, patients with such high platelet counts are not given aspirin, but given hydroxyurea first. We had one patient of CML with platelet count of 3,200,000 who presented with gum bleeding. He was treated with apheresis and hydroxyurea first.
Similar to polycythemia vera, patients older than 60 or history of thrombosis are given hydroxyurea and aspirin. All other patients receive only aspirin. Interestingly, for younger patients with no history of thrombosis and no cardiovascular risk factors, platelet reduction is not required up to even 1,500,000. There are studies to suggest, however, that patients with JAK 2 mutation are at higher risk of thrombosis, and should probably be treated to keep platelets near normal. Most of the studies do not show a correlation between platelet count and risk of thrombosis, but correlation with wbc count, Hb etc. Management of pregnancy and perioperative is same as polycythemia largely.
Long term hydroxyurea use and risk of AML transformation was considered a possibility in past. Larger studies however do not show this correlation, including in many other conditions of long term use, such as sickle cell disease. Also, hydroxyurea is shown to be better than anagrelide in all randomized trials.
Removing platelets by apheresis is of use in emergency cases, such as major CNS or lung symptoms, or bleeding with high platelet counts. We have experience with this treatment in both scenarios.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. firstname.lastname@example.org Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com