Barriers To Diagnosis In Myeloproliferative Neoplasms

Timely diagnosis of patients (pts) with polycythemia vera (PV) and essential thrombocythemia (ET) is important given the risks of thrombotic and hemorrhagic complications, disease progression and associated symptoms.  Pts often present initially to primary care physicians, who may have limited previous experience with PV/ET given the low prevalence.  Little is known about the timeliness of referral or diagnostic testing after identification of abnormal blood test results or if delays in diagnosis affect patient outcomes.

To determine the time from initial lab abnormality to referral, diagnosis and treatment of pts with PV and ET.

Pts at a single Canadian academic institution newly diagnosed with PV or ET from Jan 2010 to May 2013 were identified.  Retrospective data was collected including demographics, lab values, diagnostic testing and treatments.

Demographics: 26 pts with PV and 34 with ET were identified.  Median age was 67.5 (44-89) y for PV and 66.5 (34-92) y for ET.

Delay in Referral and Diagnosis: 98% of pts were referred directly to a hematologist by their primary care physician.  69% of PV pts were referred within 30 days and 92% within 90 days of initial lab abnormality.  Median time from referral to diagnosis was 98 (0-221) days.  41% of ET pts were referred within 30 days and 56% within 90 days of initial lab abnormality.  Median time from referral to diagnosis was 121 (8-638) days.  PV pts were referred sooner, median 20 (0-187) days, than ET pts, median 67 (0-3743) days (p=0.01).  The median delay from referral until hematology assessment was 51 days for PV compared to 78 days for ET (p=0.08).  After assessment by the hematologist, it required a median of 35 days to make a diagnosis of PV and 25 days for a diagnosis of ET (p=0.31).

Referrals by platelet (plt) count: There was a trend to earlier referral of ET pts with higher platelet (plt) counts.  15/20 (75%) ET pts with plt count >600 were referred within 90 days of initial lab abnormality whereas only 4/14 (29%) of pts with plt count 450-600 were referred within 90 days (p=0.056).

Treatment of PV pts: 22/26 (85%) pts received phlebotomy at or after referral at the direction of a hematologist.  Average delay in referral (and phlebotomy initiation) for patients treated with phlebotomy was 32 days.  13/26 (50%) pts were initiated on treatment with hydroxyurea within 2 months of diagnosis.  Average delay in diagnosis (and hydroxyurea initiation) in this subgroup was 142 days.   11/26 (42%) pts were receiving ASA prior to the initial hematological consultation.  12/26 (46%) were initiated on ASA at or shortly after hematological consultation.  Average delay to hematology consultation (and ASA initiation) was 90 days in this subgroup.

Treatment of ET pts: 8/34 (24%) pts were initiated on treatment with hydroxyurea within 2 months of diagnosis.  Average delay in diagnosis (and hydroxyurea initiation) in this subgroup was 790 days. 17/34 (50%) pts were receiving ASA prior to the initial hematological consultation.  15/34 (44%) were initiated on ASA at or shortly after hematological consultation.  Average delay to hematology consultation (and ASA initiation) was 355 days in this subgroup.

No thrombotic or major hemorrhagic complications occurred in any PV/ET pts between the time of initial lab abnormality and diagnosis.

This study demonstrates the marked variability in time from lab abnormality to referral and diagnosis for PV/ET pts.  Primary care providers were more likely to promptly refer PV pts than ET pts, and particularly tended to overlook referral and investigation of pts with modestly elevated plt counts of 450-600.  This is a concern, as risk of thrombosis in ET pts is independent of plt count.  Delays were also apparent in wait times for hematology appointments and subsequent diagnostic tests.   The delay in diagnosis led to a delay in initiation of therapy to reduce risk of thrombosis in both PV and ET pts.  Possible strategies to expedite diagnosis include targeted education of primary care physicians focusing on identification of lab features of PV/ET.  Directive comments on lab reports by community hematopathologists may also facilitate prompt referral and investigation.

No relevant conflicts of interest to declare.