Coagulation for the Neurosurgeon
Hemostasis and thrombosis are two critical physiologic concepts that are essential for neurosurgeons to understand to treat patients effectively. Poor control of either one in neurosurgery can result in significant morbidity and mortality resulting from hemorrhagic or ischemic stroke. In this chapter, we present the basic science of coagulation and describe both the classical coagulation cascade and a more modern cell-based model of coagulation that we believe is more relevant. Next, we follow with an overview of the molecular interactions that occur on platelets to induce platelet plug formation. Over the past 20 years, there has been much research directed toward developing antithrombotic drugs that focus on platelet inhibition. We present a list of current platelet inhibitors used today and describe their mechanism of action and clinical dosage. Advances in endovascular therapy in the heart and brain have led to increased use of these drugs and present a problem for neurosurgeons in the case of acute intracranial or spinal hemorrhage. We present the latest methods to reverse the effects of these drugs to arrest bleeding and provide neurosurgeons an opportunity to operate on these patients with reduced morbidity and mortality. As with antiplatelet drugs, there has been a significant increase in the number of anticoagulant drugs, especially those directed at coagulation factor Xa (FXa) and thrombin (IIa). This includes orally available FXa and thrombin inhibitors, commonly referred to as direct oral anticoagulants (DOACs). These drugs have demonstrated efficacy in preventing strokes in patients with atrial fibrillation and in treating venous thromboembolism (VTE). Manufacturers of these drugs have stated that their advantage over warfarin (Coumadin), which for years has been the mainstay of treatment, is that they do not require monitoring. Not surprisingly, these drugs present a difficult challenge for neurosurgeons as there is no reliable way to assess their activity to determine if it is safe to operate when a patient presents with intracranial hemorrhage associated with one of these medications. We present a list of anticoagulant drugs by molecular target including FXa inhibitors, thrombin inhibitors, and coumarins. We also present the tested methods of reversing the activity of these drugs where available. Given the proliferation of drugs that are effective in inhibiting thrombosis but have considerable morbidity and mortality resulting from intracranial hemorrhage, we present research that focuses on improving the efficiency of anticoagulant and antiplatelet drugs. Aptamers are DNA and RNA molecules that bind to and inhibit the activity of proteins in ways similar to monoclonal antibodies and small molecules. They have a unique advantage over other molecules in that antidotes can be rationally designed to reverse their activity. This class of drug agents may have a positive impact in reducing the morbidity and mortality associated with robust platelet inhibition or anticoagulation. Finally, we describe different intraoperative hemostatic agents such as nanoparticles and chitosan that have shown promise in aiding neurosurgeons manage bleeding during surgery.
