A Case Series of Related Bone Marrow Donors with Prolonged Prothrombin Times but No Perioperative Bleeding Complications

Background:

Sickle cell disease (SCD) is a state of chronic inflammation and hypercoagulability.  Previous studies have demonstrated that patients with SCD experience higher rates of perioperative complications when compared to normal patients.  Although SCD is considered a hypercoagulable disease, intra-operative bleeding has been reported as a significant complication. Patients with SCD who are admitted for surgical procedures often are found to have prolonged prothrombin times (PT), which may contribute to the risk of bleeding.  Matched-related donor (MRD) bone marrow transplant (BMT) offers a cure for patients with SCD.  Matched-related donors often have sickle cell trait (SCT).  We anecdotally observed multiple MRD with SCT and mild prolongation of the PT. This prompted a systematic examination of a series of MRD for coagulation values, SCT status, and the incidence of bleeding complications with the bone marrow harvest.

Methods: 

Retrospective chart review of MRD BMT donors for sickle cell disease between 1/2005- 10/2014 to compare PT, partial prothrombin times (PTT), international normalized ratio (INR), and the incidence of bleeding complications in donors with and without SCT.  Mann-Whitney and Fisher’s Exact test were used for statistical analyses.

Results: 

Twenty-five donors were included in the analysis.  Median age of donors was 9.8 years (range 2.6-25.3).  None of the donors had bleeding complications with the bone marrow harvest.  Sixteen of the twenty-five (64%) donors had SCT.  Of the 16 patients with SCT, 5(31%) had a prolonged PT, whereas only 1/9 (11%) of patients without SCT had a prolonged PT. Although the trend was suggestive, the sample size was too small to show that the difference was statistically significant (p=0.36).  There was also no significant difference in INR or PTT.  The average PT in SCT patients with prolonged PT was 15.1 seconds (14.2-16.1), and average INR was 1.23 (1.16-1.33).

Conclusions: 

Our series suggests that patients with SCT tend to have prolonged PT when compared to normal controls.  However, despite the prolongation in PT, none of the donors experienced significant perioperative complications, including bleeding.  The cause of this prolongation in PT in patients with SCT remains uncertain, but may be a result of low levels of sickling in the kidneys, mild liver dysfunction, or vitamin K deficiency.  A planned multi-center study examining coagulation values and bleeding complications in donors with and without sickle cell trait should allow confirmation of the finding that there is no increased risk of perioperative bleeding in these donors and that donors with SCT have a statistically significant increase in the incidence of prolonged PT.  That determination would be timely given the increasing numbers of patients being transplanted for SCD, many of whose related donors will have the trait.