Monday, January 3, 2011
COAGULATION CORNER: JANUARY 2011
OVERVIEW OF ASH
HAPPY AND HEALTHY 2011 TO ALL!
The annual American Society of Hematology meeting was held in Orlando Florida. There were many attendees, lots to listen to and record breaking low temperatures in Orlando!
One of the main topics of discussion was the administration of 2 recently cleared US drugs- rivaroxaban (oral direct Xa inhibitor) and dabigatran (oral direct thrombin inhibitor). These drugs are body weight dependent and are said to not require monitoring, however there are instances where they will need to be monitored. They have been in use ex-USA for about a year however clinicians expressed the following concerns. These drugs do not require monitoring clinicians are concerned that they will not know if a patient is being compliant. Patients who are starting long term anticoagulation on these drugs may stop taking the drugs after symptoms of a thrombotic event subsides. Dabigatran requires twice daily dosing making compliance more difficult. Many patients can not commit to this regimen will not be able to take the drug. Warfarin is monitored on a regular basis and compliance issues can be addressed. As a result, people failing to take the drug will be at an increased risk of thrombosis, clinicians will not have a way to determine if the drug is on board or not. They feel that there should be a way to measure levels.
Regarding monitoring of the drugs, Rivoroxaban: may be able to be monitored by an anti-Xa assay, however the curve must be made from the drug. Dabigatran: Anti-IIa drugs prolong all clot based assays. The thrombin time is too sensitive to use to monitor this anticoagulant. The APTT result will be prolonged however depending on the sensitivity of the reagents, the reaction flattens out and increasing doses will not be reflected by the APTT. As a result the clinician may continue to increase the dose of the anticoagulant and place the patient at a risk for bleeding. Also, patients with kidney disease may be at risk for over anticoagulation. There is a definite patient population that will require monitoring.
There were 2 large symposiums on Hemophilia that were well attended, and that addressed laboratory testing of factor VIII (FVIII). The importance of not only diagnosing but also monitoring FVII was discussed in detail. Reagent sensitivity is important at levels of 80% and borderline levels of 40-50%. These levels are important to reflect if the hemophiliac patient FVIII levels are stabile pre and post operatively. Elevated levels of FVIII are also important to detect an excess of infused product which can reflect supra-therapeutic levels of FVIII and place a patient at a risk for thrombosis.
Also recombinant von Willebrand factor is being developed. This will impact how vW assays are run, as well as levels of FVIII from patients who have received this product. At present a new drug Wilate is being looked at for the treatment of VWD. This is an FDA approve drug derived from human plasma, at present most centers use Humate. The take away message from this is that patients who receive this drug may not maintain levels of VWF and FVIII for as long as patients who receive Humate P. This is important for people in the field to know, since clinicians and laboratories may see greater changes (decreased levels as opposed to patients treated with Humate) in repeated measures of FVIII and VWF.
Immune thrombocytopenic purpura (ITP) is a platelet disorder that doesn’t have one specific diagnostic test. Even testing for anti-platelet antibodies may not prove diagnostic since not all ITP patients have antibodies. Since 1913 spleenectomy has with used with a 66% chance of a positive response. Rituxamab has been used with success and a thrombopoeitin receptor, Romoplostin, has been used to stimulate platelets. Also, Ettrombopog, and FDA approved drug has been found to sustain platelets for about 2-3 years, however it is an early drug and there may be future toxicity. 20% of ITP patients have a secondary etiology. H pylori and ITP seem to have a patho-physiological link, when treated for the H. pylori, there was a 50% improvement rate, with increased response rates seen in Japan and Italy, most likely due to the serotypes found in those countries. ITP occurs in pregnancy at a rate of 1:1000, and usually presents early on and is treated with IVIG.
The risk of thrombosis and cancer ranges from 1-30%. The ability to target a patient’s risk will aid the clinician in who should be treated. A scoring system based on 5 independent risk factors include the site of cancer, pre-chemotherapy platelet count, hemoglobin level, pre-chemotherapy WBC and body mass index are evaluated and placed in a low, intermediate or high risk. This can help to improve the risk benefit of anticoagulation. To prevent VTE it is important that all surgical patients are anticoagulated. Additionally many cancer patients benefit from a longer duration of prophylaxis for up to 1 month post surgery. The recommended treatment for cancer-associated thrombosis is LMWH. It is more effective than warfarin and reduces the risk of recurrent VTE by 52%.
This meeting was a wonderful opportunity to learn, network and see old friends. Hope that I have give you a piece of what was experienced-minus the cold weather!
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