Stephan Moll, MD writes…. Freshly published just now (May 2013), the 3rd edition of the very clinical-practical Consultative Hemostasis and Thrombosis textbook edited by Kitchens, Kessler & Konkle – link here. 822 pages, 47 chapters on bleeding and clotting disorders, diagnosis, management. Suitable for whom? Useful as a reference for all practicing physicians and midlevel providers who encounter patients with bleeding and thrombotic disorders. An excellent book, down to earth, clinically useful, detailed and yet focussed, not detached or esoteric; very user-friendly. I highly recommend it.
Disclosure: I am author of a chapter in this book, but have no financial conflict of interest.
Last updated: May 17th, 2013
Stephan Moll, MD writes….
The pharmaceutical company Portola reported today (May 8th, 2013) without many details on the findings of their phase 2 human volunteer study of their anti-Xa anticoagulant antidote PRT4445 – ClinicalTrials.gov Identifier: NCT01758432 (study description here). In this study, healthy volunteers who had taken Eliquis (Apixaban) received the antidote. The study showed a “rapid and sustained and dose-related reversal of the anticoagulant activity of Eliquis” (thrombin generation and anti-factor Xa activity) and “no serious adverse events”.
PRT4445 is a recombinant molecule, structurally very similar to native factor Xa, but with some modifications that make it inactive as a clotting factor. It acts as a decoy for factor Xa inhibitor drugs, binding them. Once they are bound they are unable to bind to and inhibit native factor Xa. Thus, the native factor Xa becomes available to participate in the coagulation process and normal hemostasis is restored.
The full Portola report is here. The data of the study still need to be presented at a medical meeting and published. At this point all that can be concluded is that the drug is reported to have an ex vivo effect on coagulation tests. Whether it has any clinical efficacy in major bleeding associated with Eliquis or any of the other new oral anti-Xa anticoagulants (Xarelto=rivaroxaban; Edoxaban) has yet to be investigated.
Disclosure: I have consulted for Janssen, Boehringer-Ingelheim, and Daiichi.
Last updated: May 8th, 2013
Patients not infrequently inquire about the benefit of “natural blood thinners”. Clot Connect has written a document for patients – available here – discussing the various herbs and dietary supplements that are often called “natural blood thinners”. The blog post discusses many items including garlic, gingko, chocolate, fish oil, vitamin D, vitamin E, etc. The health care professional may want to be familiar with these herbs and supplements and the laboratory and few clinical data behind them, to be able to respond to patients initiating discussion about the potential usefulness of these products.
Stephan Moll, MD writes… A new drug for the urgent reversal of warfarin was approved by the FDA today, April 29th, 2013 (announcement by the FDA is here), called Kcentra. The drug is derived from pooled plasma from healthy blood donors and contains the coagulation factors that are low in warfarin-treated patients, i.e. factors II, VII, IX, and X. It is also referred to as a 4-factor concentrate, or non-activated Prothrombin Complex Concentrate (PCC). The drug prescribing information (package insert) is here.
Up until now only 3-factor concentrates (PCC) and fresh frozen plasma (FFP) were available in the U.S. in addition to vitamin K to urgently reverse warfarin and to treat major bleeding in warfarin-treated patients. The new drug is a welcome addition to the armamentarium when having to treat warfarin-associated major bleeding. Where until now I used to give 3-factor PCCs, I will from now on give the 4-factor PCC.
Bleeding and the new oral anticoagulants
A question that will now be raised is whether this new drug is also suitable to treat major bleeding on one of the new oral anticoagulants, i.e. Xarelto, Pradaxa, or Eliquis. It is not known whether Kcentra would be beneficial in that situation. However, as some hospitals and clinicians presently have 3-factor PCCs on their reversal algorithm, it is fair to consider a review and possible modification of the hospital treatment guidelines on the management of major bleeding not only on warfarin, but also on the new oral anticoagulants.
Am J Hematol 2012;Volume 87 (Suppl 1):S181 (abstract).
Disclosure: I have no financial conflict of interest
Last updated: April 30th, 2013
Stephan Moll, MD writes… The decision how long to treat a patient with venous thromboembolism (VTE) with anticoagulants can often be made based on the patient’s history alone, i.e. the circumstances of the VTE event (provoked versus unprovoked). Often, no thrombophilia testing is needed. However, if one were to do thrombophilia testing, what is the right time to test? Read the rest of this entry »
Stephan Moll, MD writes…
Reversal of anticoagulation for the patient presenting to the Emergency Department with major bleeding on an anticoagulant or with markedly elevated INRs on warfarin may be needed. This issue may best be addressed in a health care system by the establishment of a structured treatment algorithm/guide. Here is, in one document, the treatment guide and reversal strategy established for the ED at our institution Read the rest of this entry »
Stephan Moll, MD writes…
Occasionally, recurrent DVT or PE occur in spite of warfarin therapy, particularly in patients with (a) fluctuating and sub-therapeutic INRs, (b) lupus anticoagulant/ antiphospholipid antibody (APLA) syndrome or (c) cancer. Read the rest of this entry »
Stephan Moll writes…
2012 has been a year with significant progress in the field of venous thromboembolism and anticoagulation. The three most noteworthy, clinically relevant developments were probably (a) the publication of the new ACCP (American College of Chest Physician) guidelines on antithrombotic therapy in February 2012; (b) The FDA-approval of rivaroxaban (Xarelto) in November 2012 for the acute treatment of venous thromboembolism (VTE) and long-term secondary prevention; and (c) The FDA-approval of apixaban (Eliquis) in December 2012 for atrial fibrillation and the prevention of arterial thromboembolism. Here I have listed and summarized the 10 top publications of 2012 in the field of venous thromboembolism and anticoaguation as I see them – the ones clinically most relevant.
Disclosure: I have consulted for Janssen, Boehringer-Ingelheim and Daiichi.
Last updated: Feb 7th, 2013
Stephan Moll, MD writes…
Apixaban (Eliquis®) is FDA-approved for the prevention of stroke and systemic arterial thromboembolism in patients with atrial fibrillation (Clot Connect discussion of the approval on Dec 28th, 2012 is here). Here is the management guideline for apixaban Read the rest of this entry »
Stephan Moll, MD writes…
Xarelto® is FDA approved for treatment of venous thromboembolism (VTE), prevention of VTE after hip and knee replacement surgery, and for atrial fibrillation. A number of practical management questions are encountered by physicians, pharmacists, and other health care professional taking care of patients on Xarelto®, such as (a) dosing in renal impairment, (b) conversion of a patient on warfarin to Xarelto®, (c) discontinuation of Xarelto® at times of surgery, dental procedures, colonoscopy, and other procedures, and (d) management of bleeding on Xarelto®. These issues may best be addressed in a health care system by the establishment of a structured treatment algorithm/guide/help for the entire hospital or physician practice. Read the rest of this entry »