Monday, August 3, 2009
OVERVIEW OF ISTH: 2009
INTERNATIONAL SOCIETY OF THROMBOSIS AND HEMOSTASIS
BOSTON - 2009
The British are coming! echoed Paul Revere through the streets of Boston-
Well, during the week of July 11th, Boston was invaded with people interested in the field of coagulation. Not only were hematologists, laboratory and research personnel attended, but there were also cardiologists, trauma surgeons, and ER physicians present. The scope of coagulation has invaded many other disciplines.
The week begins with the Subcommittees that meet and cover topics from fibrinolysis to women's health to lupus anticoagulants. If you want to read there minutes, they are posted on the ISTH website; .and can be a great resource. The only problem with this meeting is that it is like a giant buffet, you have to pick and choose from an extensive menu, and you want to sample everything! Plus there are the exhibits, and posters and you never want to miss the flavor of the city!
The first subcommittee was Factor VIII and Factor IX and a discussion on the 1 stage versus 2 stage assay for factor VIII. One-stage is the assay used by laboratories. Most routine labs do not use the 2 stage assay, so they compared it to the chromogenic assay. There are certain mutations that will cause the one stage versus chromogenic assay to have a ratio > 2.0, which means you can miss a mild hemophiliac. There have been 28 mutations identified. These patients clinically bleed. This is important to understand, and depending on your patient population, may need to also have a chromogenic assay on board.
Ever popular are the D-dimer sessions. Everyone is still trying to predict how you can tell who will have a recurrent thrombotic event and what factors may contribute to it.
It was found that gender did not play a role in provoked VTE; however males had an increased risk of occurrence in unprovoked incidences, also being a male under the age of 50 also increased the risk. Patients, who had a negative d-dimer a VTE, had a lower recurrence rate, as opposed to those who had a positive d-dimer. Patients having a positive d-dimer 1 year out can result in a recurrence rate of 12 versus 2.2 in patients with a negative d-dimer. If after you remove a patient from oral anticoagulation and the d-dimer is elevated 1 month post, you still have a 99% risk of reoccurrence. Let us not forget that the d-dimer increase about 10%/ decade.
The subcommittee on DIC had a great lecture on trauma and coagulation. Hemorrhage accounts for 40% of death in trauma. There are issues with dilution of factors because of the fluids and plasma rapidly give and consumption of factors. In as study that looked at 5000 trauma patients it was noted that patients that presented with a PT of > 22 seconds resulted in increased mortality. Also decreased Protein C levels are associated with shock, with an increase in Activated Protein C. It is important to look at a patient's blood smear to look for microangiopathic anemia.
Cardiovascular genetics looked at increased levels of LDL (remember this is lousy cholesterol, and should be low) versus HDL (which is happy cholesterol and should be high). The in a 15 fold increase in cardiovascular disease (CHD) in the US versus pre-industrial countries. Every mg/dl decrease in LDL decreases the risk of CHD by 1%, therefore lowering LDL from 271 to 236 lowers CHD by 26%. Understanding the genetic traits for LDL, as well as the gene metabolism that is involved in LDL production can aid in developing preventative medicine and improve public health.
Heparin-induced thrombocytopenia or HIT is an immunologic adverse effect of heparin therapy causing antibody mediated platelet activation and thrombin generation. That is the drug that is supposed to prevent clotting has now caused a clot. Patients should be diagnosed based on the negative predictive value of clinical tests and the clinical picture. Patients will have a 50% drop in platelet count and a new thrombosis. On a first exposure to heparin this will occur on the fourth day, however, if a patient had been previously exposed to heparin, even in small doses it will happen in 1-2 days. Thrombocytopenia occurs from intravascular platelet activation. The pathogenic immunoglobulin isotype is IgG. Anti-PF4/heparin antibodies bind to PF4 via their F(ab) domains. The lead to formation of large immune complexes that cross=link the platelet FcyIIa receptors causing platelet aggregation. The negative predictive value of assays is a good tool in ruling out HIT. Using polyspecific IgGAM assays have a specificity of about 50-75%, while using an IgG Elisa can enhance up to 90%. A good tool in patient assessment is using the 4T scoring system: Thrombosis, Thrombocytopenia, Time and oTher. Combining the score and the laboratory test for HIT provides the highest predictive value.
Now, on to platelets and how to inhibit them! Aspirin has been around for 110 years and works by acetylating platelet cyclooxygenase (COX-1) inhibiting thromboxane production. The trick is to use the lowest dose that is effective without causing a GI bleed. Aspirin reduces major vascular events by 12%, however, it was noted that aspirin seems to be less effective in the diabetic patient. The new P2Y12 blockers ware ADP receptors that work by inhibiting ADP induced platelet aggregation, which has been shown to decrease the risk of arterial occlusion. Thienopyridines are a class of drugs which irreversibly inhibit P2Y12 function lasting about 8-10 days, or the lifespan of a platelet. Since its effect is irreversible it presents a problem in patients requiring emergent coronary bypass surgery. Clopidogrel treatment up to 4-5 days prior surgery has been associated with increased bleeding and hospital stays. Prasugrel a new thienopyridine is detected in plasma within 15 minutes and reaches maximum concentration within 30 minutes. The difference between these drugs is Prasugrel is more effective in converting from a pro-drug to and active metabolite. A phase III multicenter clinical trial is in progress to determine the safety and efficacy of the 2 drugs and their ability to reduce the risk of cardiovascular death, MI or stroke.
So, as you can see this is just a small insight of what goes on at a congress. There are lectures and posters and exhibits that can satisfy every coagulation pathway that you choose- whether it be platelets, factors, new research, von Willebrand disease or just the interaction among colleagues. It is truly an amazing experience one that I have been privileged to attend- just to mark your calendars, in 2011 ISTH meets in Kyoto, Japan!
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