hirudin and Subarachnoid-Hemorrhage

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

A 50-year-old patient presented with clinical symptoms of heart failure with orthopnoe and edema (NYHA IV).. Echocardiography revealed a dilated left ventricle with severely reduced left ventricular function and biventricular floating thrombi, due to dilatative cardiomyopathy.. With a heart failure medication clinical symptoms reduced and body weight decreased > 10 kg in 3 weeks. Due to the high-risk constellation, anticoagulation was performed with lepirudin and the biventricular thrombi were dissolved within 17 days. At this point in time, the patient suffered from petechial bleedings, hemoptysis and gross hematuria. Despite breaking anticoagulation and substitution of PPSB with not measurable fibrinogen, subarachnoid hemorrhage occurred leading to exitus letalis.. Lepirudin is a highly effective anticoagulant, that can induce severe hemorrhagic side effects in individual cases. The present case report demonstrates an immunological reaction as a rare cause with activation of prothrombin and formation of fibrin.

Topics: Antibody Formation; Cardiomyopathy, Dilated; Dose-Response Relationship, Drug; Echocardiography; Fatal Outcome; Fibrinolytic Agents; Heart Failure; Heart Ventricles; Hematuria; Hemoptysis; Hirudins; Humans; Male; Middle Aged; Prothrombin Time; Purpura; Recombinant Proteins; Subarachnoid Hemorrhage; Thrombosis

We observed that the second application of cerebrospinal fluid (CSF) from subarachnoid hemorrhage (SAH) patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application. It was hypothesized that the difference between the first and second applications of SAH CSF was due to the activity of thrombin.. Canine vertebrobasilar artery was removed under general anesthesia, cut into rings, and suspended in tissue culture baths so as to measure isometric tension. CSF was taken from patients 1 to 3 days after SAH via ventricular drains. CSF was administered in 10(-5) to 10(-1) dilutions. The thrombin antagonist hirudin (5 U) was administered before CSF in some experiments. The arterial tension response to pure oxyhemoglobin (10(-4) to 3.2 g/dL) and thrombin (10(-4) to 3.2 U/mL), administered alone or in combination, was also examined.. Hirudin increased arterial tension generated on the initial application of SAH CSF but had no effect on the tension generated by the second application of the SAH CSF, suggesting that thrombin limits the tension generated by vasoconstrictive agents in the CSF. Thrombin and pure oxyhemoglobin administered together produced less tension than that generated in response to oxyhemoglobin administered alone; no additive response was observed by coadministering the 2 vasoconstrictive agents.. In the presence of oxyhemoglobin, thrombin acts to reduce cerebral arterial tension. This interaction between thrombin and hemoglobin may account for the observation that the second application of CSF from SAH patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application.

Topics: Animals; Basilar Artery; Cerebrospinal Fluid; Dogs; Haplorhini; Hirudins; Humans; In Vitro Techniques; Oxyhemoglobins; Subarachnoid Hemorrhage; Thrombin; Vasoconstriction