The relationships between factor VIII associated activities, platelet function, and venous thrombosis were studied in 18 patients with lower limb paralysis following acute spinal cord injury (SCI). Deep vein thrombosis (DVT) was detected in 13 patients (72%). Eight of the 13 thromboses were documented between 6 and 8 d following injury while the other five episodes were noted on days 11 (two), 13, 18 and 22. The detection of thrombosis was preceded by marked increases in VIIIR:Ag and VIII:RCoF whereas VIII:C was only marginally increased. The platelet aggregation response to collagen was hyperactive by the sixth day while the platelet aggregate ratio (PAR) did not become abnormal until after DVT was detected. These studies suggest a chronology in the series of events leading to DVT in patients with lower limb paralysis following SCI. Initial elevations in VIII:Ag and VIII:RCoF are followed in sequence by increased platelet responsiveness to collagen, the occurrence of DVT, and the appearance of circulating platelet aggregates. Conceivably, VIIIR:Ag elaborated by endothelial cells alters platelet reactivity and provides an important determinant for venous thrombosis.
Homocysteine thiolactone (HTL) elicits seizures in mice at a dose of 850 mg/kg (95-100% of animals) with an average latency time of 19.5 min. These seizures are reversed by both 5' N-ethylcarboximide adenosine (NECA) and flunitrazepam, with respective ED50 doses of 0.025 and 0.20 mg/kg. NECA was approximately four-fold more potent as an inhibitor of HTL-induced seizures than of seizures induced by pentylenetetrazol (PTZ, 75 mg/kg). Flunitrazepam was equipotent in both seizure paradigms. The purine precursor 5-amino-4-imidazole carboxamide riboside, (AICAr), although virtually ineffective against PTZ-induced seizures at doses greater than 1 g/kg, was able to inhibit HTL-induced seizures with an ED50 of approximately 350 mg/kg. The anticonvulsant effect of AICAr was dose and time dependent. The anticonvulsant potency of AICAr was increased by simultaneous administration of the adenosine uptake blocker Mioflazine, whereas the central nervous system (CNS)-impermeable adenosine uptake blocker dipyridamole had no effect. The ability of AICAr to permeate the blood-brain barrier (BBB) is limited (less than 1%) and may explain its low potency as an anticonvulsant. AICAr also has very low potency at brain adenosine A1 and A2 receptors as well as adenosine uptake sites (IC50 greater than 10(-3) M), suggesting that its anticonvulsant properties are not mediated by direct action at these sites. The results indicate that AICAr does have frank anticonvulsant effects and further suggest that HTL-induced seizures may represent a useful paradigm for evaluation of adenosinergic agents. AICAr or more potent derivatives thereof may represent a new class of anticonvulsants with the ability to target seizure foci selectively.
To determine the extent to which autologous blood that has been donated in advance ("predeposited") is used in patients undergoing elective surgery and to assess whether predonation decreases the use of homologous blood and the demand on the blood supply, we studied 4996 patients undergoing elective surgery at 18 tertiary care hospitals. Cross-matched blood was ordered for 1287 patients (26 percent), and of these, 590 (46 percent) were considered eligible for predepositing blood. Only 5 percent (32) of the eligible patients actually predeposited blood, indicating that predonation is not widely used. Of those who predeposited, only 13 percent (4 of 32) subsequently received homologous blood, as compared with 36 percent (199 of 558) of those who did not predeposit (P less than 0.01). Among the 199 patients who did not predeposit but required transfusion, we estimate that predonation could have avoided homologous transfusion in as many as 68 percent. If all eligible patients had predeposited autologous blood, they could have supplied as much as 72 percent of their own transfused red cells. The blood for as much as 10 percent of all red-cell transfusions could have been predonated by and transfused into the patients undergoing elective surgery. Greater use of predonation would not only reduce the demand on the blood supply by decreasing the need for homologous transfusion, but would probably also reduce the risk of hepatitis and other transfusion-associated illnesses.
Abstract. Deep Vein thrombosis is very common in spinal cord injury patients, and a randomized study comparing the prophylactic use of external pneumatic calf compression, aspirin and dipyridamole has been carried out.Key words: Deep vein thrombosis; Spinal injury; Platelets; Factor VIII.DEEP vein thrombosis (DVT) occurs frequently in patients with a history of recent trauma or surgery, especially when followed by prolonged immobilisation (Sevitt & Gallagher, 1961;Sevitt, 1969). Therefore, it would be anticipated that the incidence of DVT would be high in individuals with acute spinal cord injury (SCI). Recently, we reported the presence of DVT in 13 of 18 consecutive patients with complete lower limb paralysis (Rossi et at., 1980). As compared to those without thrombosis, patients with DVT had more elevated levels of the von Willebrand factor (ristocetin-cofactor, VIII: RCof ) and factor VIII related antigen (VIIIR: Ag), hyperactive platelet aggregation responses to collagen, and the appearance of circulating platelet aggregates coincident with the detection of thrombosis. We have now had the opportunity of examining the effect of prophy lactic measures on the incidence of DVT and the above-mentioned haemostatic factors. MethodsA prospective clinical trial of DVT prophylaxis was carried out in 28 con secutive patients with acute SCI and complete lower limb paralysis; all were male except four. Subjects were randomised to one of two regimens: external pneu matic calf compression (EPCC) alone in IS, and EPCC combined with aspirin (ASA), 300 mg bid, and dipyridamole (Dip) 75 mg tid in 13. EPCC was admini stered using a Jobst Athrombic Pump (Model 66-20, Toledo, Ohio) set for I min cycles with IS sec calf compression at 40-45 mmHg.DVT was detected by daily monitoring of the legs for the local uptake of
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