Coagulation and Thrombosis-Related Research

DMB (May-June 2016)

1. A Multinational Trial of Prasugrel for Sickle Cell VasoOcclusive Events

BACKGROUND: Sickle cell anemia is an inherited blood disorder that is char- acterized by painful vaso-occlusive crises, for which there are few treatment options. Platelets mediate intercellular adhesion and thrombosis during vaso-occlusion in sickle cell anemia, which suggests a role for anti- platelet agents in modifying disease events. 

METHODS: Children and adolescents 2 through 17 years of age with sickle cell ane- mia were randomly assigned to receive oralprasugrel or placebo for 9 to 24 months.The primary end point was the rate of vaso-oc- clusive crisis, a composite of painful crisis or acute chest syndrome. The secondary end points were the rate of sickle cell–related pain and the intensity of pain, which were assessed daily with the use of pain diaries. 

RESULTS: A total of 341 patients un- derwent randomization at 51 sites in 13 countries across the Americas, Europe, Asia, and Africa. The rate of vaso-occlusive crisis events per person-year was 2.30 in the pra- sugrel group and 2.77 in the placebo group (rate ratio, 0.83; 95% confidence interval, 0.66 to 1.05; P=0.12). There were no sig- nificant differences between the groups in the secondary end points of diary-reported events. The safety end points, including the frequency of bleeding events requiring medi- cal intervention, of hemorrhagic and non- hemorrhagic adverse events that occurred while patients were taking prasugrel or placebo, and of discontinuations due to pra- sugrel or placebo, did not differ significantly between the groups.

CONCLUSIONS: Among children and adolescents with sickle cell anemia, the rate of vaso-occlusive crisis was not significantly lower among those who received prasugrel than among those who received placebo. There were no significant between-group differences in the safety findings. (Funded by Daiichi Sankyo and Eli Lilly; number,NCT01794000.)

Heeney M, et al. N Engl J Med 2016 Feb 18; 374:625-635. DOI: 10.1056/NEJMoa1512021

2. Preoperative Chemoprophylaxis Is Safe in Major Oncology Operations and Effective at Preventing Venous Thromboembolism.

BACKGROUND: We prospectively evaluated the safety and efficacy of adding preoperative chemoprophylaxis to our insti- tution’s operative venous thromboembolism (VTE) prophylaxis policy as part of a physi- cian-led quality improvement initiative. STUDY DESIGN: Patients undergoing major cancer surgery between August 2013 and January 2014 were screened according to service-specific eligibility criteria and tar- geted to receive preoperative VTE chemo- prophylaxis. Bleeding, transfusion, and VTE rates were compared with rates of historical controls who had not received preoperative chemoprophylaxis.

RESULTS: The 2,058 eligible patients who underwent operation between August 2013 and January 2014 (post-intervention) were compared with a cohort of 4,960 patients operated on between January 2012 and June 2013, who did not receive preoperative VTE chemoprophylaxis (pre-intervention). In total, 71% of patients in the post-intervention group were screened for eligibility; 82% re- ceived preoperative anticoagulation. When compared with the pre-intervention group, the post-intervention group had significantly lower transfusion rates (pre- vs post-inter- vention, 17% vs 14%; difference 3.5%, 95% CI 1.7% to 5%, p = 0.0003) without signifi- cant difference in major bleeding (difference 0.3%, 95% CI -0.1% to 0.7%, p = 0.2). Rates of deep venous thrombosis (1.3% vs 0.2%; difference 1.1%, 95% CI 0.7% to 1.4%, p < 0.0001) and pulmonary embolus (1.0% vs 0.4%; difference 0.6%, 95% CI 0.2% to 1%, p = 0.017) were significantly lower in the post- intervention group.

CONCLUSIONS: In patients undergoing major cancer surgery, institution of a single dose of preoperative chemoprophylaxis, as part of a physician-led quality improve- ment initiative, did not increase bleeding or blood transfusions and was associated with a significant decrease in VTE rates. 

Selby LV, et al. J Am Coll Surg. 2016 Feb;222(2):129-37. doi: 10.1016/j.jamcoll- surg.2015.11.011. Epub 2015 Dec 15.

Product Q&A from Our Major Sponsor

Q: The more I look into Boluoke®, the more health benefits I find. It’s interesting that Boluoke® also in- hibits the angiogenesis process. I have a patient who has a fibroid of 10cm in width. Her MD is urg- ing her to take her uterus out be- fore it takes over. She would like to try naturopathic medicine for 2-3month before the surgery. I put her on DIM, flax seed extract, iron, Femalance, liver support. And I am looking for an enzyme to help digest fibroid debris a bit as per Dr. Tori Hudsen. Would Boluoke® help with fibroid for its enzymatic properties and angiogenesis inhibition? Thanks!!

F. Wang, ND (Calgary, AB)

A: With treating uterine fibroid, it re- ally depends on the following factors: 1).Is it causing any symptoms? e.g.heavy menses, digestive discomfort, or constipation; 2). Is it growing fast? If the fibroid does not have any of the above issues, then you’ll have more time to treat it.As for Boluoke®, I am not sure if it’ll help with U. fibroids, which are hypertrophied uterine muscles, not fi- brin deposits.There is no research data to show that it will help. Unless your patient has hypercoagulation, then you can use Boluoke®. Otherwise, I would not recom- mend it. Having said that, Dr. Tori Hudson’s recommendation may still work, because theoretically systemic enzyme therapy may help by lowering the overall inflammation

Q: I am a DC who practices func- tional medicine and I recommend Boluoke® to patients when appro- priate. In 2011 and 2013 I suffered from bilateral PE’s. Both episodes were preceded (by a week or two) by infections of the same type, possibly babesia, although I am not sure. I also had high homocysteine levels

A: Because of your PE history, your preven- tative dosage for Boluoke® is likely about 1 cap 3 times daily. However, to establish a true maintenance dose, the following is the process we recommend:

1. If you intend to stop Coumadin, you may start Boluoke® immediately afterwards (initial dose depends on the thrombembo- lism risk; a clinical judgement)

2. Assess the effectiveness of the protocol after 3 weeks by doing proper testing: Option1: Sonoclot® test (an in office test- ing)

Option2: Prothrombin Fragment 1+2, Thrombin/Antithrombin Complex, Alpha- 2-Antiplasmin, Fibrinogen (via major labo- ratories like Quest or LabCorp).

3. Depending on the results of the test, ad- just the dosage of Boluoke®.
4. Re-Assess the effectiveness of the new protocol after another 3-4 weeks.

5. Adjust the dosage again if necessary.
6. You should be able to settle on a main- tenance dosage after 2-3 cycles of testing- adjusting-dosage.
7. After a maintenance dosage has been es- tablished, then periodic re-assessment may be appropriate (e.g. every 3-6 months).
8. In time of stress (e.g. infection, inflam- mation, trauma), the dosage may need to be adjusted upwards to provide additional protection until the stress is over. Boluoke® effectiveness does not decrease even when you use it for long term.There is at least two long-term (i.e. 2 years) stud- ies that looked at using lumbrokinase as a secondary prevention of stroke.