Biotech Primer article: Meds for Thinner Blood Can Equal Fewer Clots, But How?
STOPPING A BIG PROBLEM: BLOOD CLOTS
July 13, 2017
Original article can be found here.
MEDS FOR THINNER BLOOD CAN EQUAL FEWER CLOTS, BUT HOW?
The FDA’s recent approval of Portola Pharmaceuticals’ (South San Francisco, CA) new blood thinner drug Bevyxxa paved the way for the prevention of blood clots in patients hospitalized for conditions such as heart failure, stroke, and pulmonary disease. The medical term for blood clot is venous thromboembolism (VTE), but if we take it apart:
- “venous”means relating to a vein or the veins.
- “thrombo” is a blood clot.
- “embolism”involves the lodging of an embolus, a blockage-causing piece of material, inside of a blood vessel.
Hospitalized patients are at high risk for VTE because of their restricted mobility — not being able to move causes blood to pool and collect in the body. An especially dangerous type of VTE is deep vein thrombosis — blockage of a vein that is deep within the body, as opposed to near the surface of the body. If a portion of a deep vein thrombosis breaks off, it may travel to the lungs, causing a potentially fatal pulmonary embolism.
An estimated 24 million people are hospitalized annually due to VTE, so let’s find out how blood clotting is activated and learn the science of Bevyxxa.
A CLOT IN THE DARK
In healthy people, blood clotting is activated when tissue or a blood vessel is damaged, and involves specialized blood cells known as platelets — also known as thrombocytes. Either type of aforementioned damage results in activating platelets, which then form an initial “plug” at the site of injury. At the same time, proteins known as clotting factors are also activated. Clotting factors work together to produce a protein called fibrin, which is a fiber-like protein that forms a network of strands that, together with the platelets, form a clot at the site of injury. Clot formation in response to injury prevents excessive bleeding and enables healing to begin.
VTE occurs when blood clots form in the absence of an injury. These clots may break free and migrate to another part of the body, where it may interfere with blood circulation and impair organ function. If this occurs in a major organ such as the lungs, brain, or heart, critical injury or death may result. The clots may also grow to a size large enough to block the flow of blood in the blood vessel in which it originally developed. Risk factors for VTE may be acquired (including older age, major surgery, prolonged immobilization, certain type of cancers, pregnancy and hormonal contraceptives) or inherited.
MECHANISM OF ACTION: BEVYXXA
Bevyxxa and other drugs that prevent the formation of blood clots belong to a class of drugs called anticoagulants which thin the blood. Bevyxxa works by directly inhibiting one of the key clotting factors, Factor Xa. This differs from older anticoagulants such as warfarin that works by inhibiting Vitamin K, which is required for complete activation of clotting factors.
Some key benefits of direct Factor Xa inhibition include faster onset, less interaction with other medicines or certain foods, and fewer bleeding events observed during clinical trials, leading to a better safety profile. Bevyxxa is the first oral Factor Xa inhibitor to be approved, and has been approved for use for up to 42 days. These attributes mean Bevyxxa can be prescribed to a patient to continue taking the anticoagulant after release from the hospital.
Patients were selected for treatment with Bevyxxa based on increased levels of “D-dimers” in their blood. D-dimers are degradation products of fibrin, the key protein component of blood clots. When our body breaks down blood clots, D-dimers are produced. Thus, having higher than normal blood levels of D-dimers is a sign that higher levels of blood clots are present.
AN ANTICOAGULANT U-TURN
Anticoagulant drugs can be life-saving; however their inhibitory effects may need to be reversed due to major bleeding, or in the case of an emergency surgery. Portola’s andexanet alfa, currently in late stage development, reverses Factor Xa inhibition. Andexanet alfa works by irreversibly binding Bevyxxa, preventing it from binding clotting Factor Xa. If Bevyxxa can’t interact with and inhibit Factor Xa, it no longer prevents blood clotting.
COCKTAIL FODDER: BLOOD THINNERS IN THE WILD
Ever wonder how mosquitos and ticks are able to keep the blood flowing from their point of attack until they’ve had their fill? It turns out that their saliva contains a natural anticoagulant which prevents platelets from being activated. Fortunately, the effect is only temporary and localized to the site of the insect bite.
Foods that we eat may also impact blood clotting ability. For example, foods high in vitamin E such as almonds and hazelnuts, as well as spices such as cayenne pepper, garlic, ginger, and onion have some natural anticoagulant effects, while foods high in vitamin K such as leafy green vegetables, egg yolk, and soybeans may promote coagulation. For most healthy people, the relatively small amounts of these foods consumed in a normal diet would not have a significant impact on blood clotting; however, those on anticoagulant medicines may want to consult their physician about any possible dietary impact on their medicine’s efficacy.