refludan and Blood-Coagulation-Disorders

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Cerebral Hemorrhage; Hemorrhage; Hirudins; Humans; Peptide Fragments; Protein C; Recombinant Proteins; Vitamin K; von Willebrand Factor

Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.

Topics: Acute Disease; Adenosine Diphosphate; Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Platelets; Brain; Brain Injuries; Hirudins; Kinetics; Male; Partial Thromboplastin Time; Platelet Aggregation; Prothrombin; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Subarachnoid Hemorrhage; Thrombelastography; Thrombin; Wounds, Nonpenetrating

Topics: Animals; Antibody Formation; Anticoagulants; Blood Coagulation Disorders; Dogs; Hirudins; Humans; Male; Rats; Recombinant Proteins; Swine; Thrombin; Thrombosis