Will your drug have an effect on hemostasis?
The drug development process entails rigorous testing to ensure both efficacy and safety of each new drug candidate. During pre-clinical and clinical studies, drug manufacturers work diligently to reveal unknown side effects that could be harmful to patients. One of the most prominent, and dangerous, side effects is when a drug candidate interferes with a patient’s blood coagulation system — or hemostasis. This could result in either a hypocoagulable state (bleeding) or a hypercoagulable state (blood clots), which puts the patient at risk of serious complications or even death. This is especially concerning when the disease being treated already has a negative effect on the hemostatic system, such as certain types of cancer.
Hemostasis-related side effects are one of the largest contributors to drug candidate derailment and market withdrawal costing drug manufacturers millions of dollars. Luckily, there are a number of assay techniques that can be employed during the pre-clinical and clinical phases to assess the risk of hemostasis-related side effects caused by a drug candidate.
Thrombin Generation Assay (TGA) – The thrombin generation assay measures the overall hemostatic potential of a plasma sample. Unlike traditional clotting assays, such as PT and aPTT, which measure thrombin formation only during the initiation phase of coagulation, TGA measures thrombin formation throughout the entire clotting process. Since the majority of thrombin is generated after initiation, TGA provides a broader picture of total clotting potential. As such, it can be predictive of a patient’s bleeding or thrombotic risk. The TGA can be used pre-clinically by adding samples of your drug to plasma and measuring the effect that that drug may have on plasma. Clinically, the TGA can be used to evaluate patient plasma samples throughout the study to identify any coagulation abnormalities.
Thromboelastography (TEG) – Thromboelastography is a quantitative assay that measures the ability of whole blood to form a clot. It does this by measuring the viscoelastic changes caused by fibrin polymerization, the rate of clot formation, and the strength and stability of the resulting clot. In this way, a comprehensive insight into the patient’s coagulation state is achieved, and the effects of a drug can be quantified.
Platelet Aggregometry – This technique evaluates the rate at which platelets clump together to form a clot. This method can be used to detect increases or decreases in platelet aggregation attributable to the introduction of a drug product.
PT and aPTT – Prothrombin time (PT) and activated partial thromboplastin time (aPTT) assays are used to detect hemostasis efficacy in the extrinsic and intrinsic pathways of coagulation. Using these general coagulation assays, a drug’s effect can be seen and narrowed to one of the two pathways.
Coagulation Factor Assays – Factor assays evaluate the contribution of each individual coagulation factor in a whole blood or plasma sample to hemostasis. Through the evaluation of individual factors it is possible to hone in on where a drug candidate is having the effect.
How Haemtech can help
We have over 30 years experience in blood coagulation and hemostasis. We specialize in running each of these methods to identify, understand and potentially mitigate negative hemostatic effects related to your drug product. We can assist you from IND through batch release to get your product to market faster — and safer.
Haemtech Biopharma Services is a QC/Clinical testing laboratory operating under cGMP/CLIA guidelines. Data is timely, accurate and fully supported for regulatory submission.
- FDA inspected/registered
- EMA certified for GMP