Assessment of common nonsteroidal anti-inflammatory medications by whole blood aggregometry: a clinical evaluation for the perioperative setting.

OBJECTIVE: To help define the perioperative risk related to commonly used non-aspirin NSAIDs with whole blood platelet aggregometry. METHODS: Twelve healthy volunteers were recruited. Two cyclooxygenase (COX)-1 inhibitors (ibuprofen and naproxen) and two COX-2 inhibitors (meloxicam and celecoxib) were administered, and daily whole blood platelet aggregometry studies were obtained until studies showed no platelet inhibition. Aspirin was studied at the conclusion of the study. RESULTS: Ibuprofen had no inhibitory effect on platelet aggregation in all women and no inhibitory effect in 83% of men at 24 hours. All platelet function had returned to normal at 48 hours. The inhibitory effect of naproxen on platelets was absent at 48 hours in 83% of the women and 50% of men. By 72 hours all platelet studies had returned to normal. Meloxicam and celecoxib did not cause any overall inhibitory effect on platelet aggregation. CONCLUSIONS: Ibuprofen and naproxen have a mild inhibitory effect on platelet aggregation compared with aspirin and this effect is undetectable by 48 hours and 72 hours, respectively. Meloxicam and celecoxib show essentially no inhibitory effect on platelet aggregation. These findings suggest that there is little bleeding risk related to platelet aggregation at 24 hours in patients who take COX-2 inhibitors and at 72 hours for those who take COX-1 inhibitor medications.

Intracranial phosphaturic mesenchymal tumors: report of 2 cases.

Hypophosphatemia with osteomalacia may be due to a neoplasm that produces fibroblast growth factor 23 (FGF-23), which inhibits phosphate reabsorption in the kidneys. Most of these tumors occur in bone or soft tissue and occasionally in the head, although intracranial occurrence is very rare. This report describes a tumor that caused hypophosphatemia and osteomalacia and was located entirely in the right anterior cranial fossa. Radiologically, the tumor resembled a meningioma; histologically, it was a low-grade phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). After gross-total resection, the patient's symptoms abated and laboratory values normalized. The authors also studied another PMTMCT initially diagnosed as a hemangiopericytoma that involved the left anterior cranial fossa and ethmoid sinus, and reviewed reports of 6 other intracranial tumors that induced osteomalacia, 3 entirely in the anterior cranial fossa, 2 involving the anterior cranial fossa and ethmoid sinus, and 1 in the cavernous sinus. In older children or adults who have hypophosphatemia with osteomalacia and no personal or family history of metabolic, renal, or malabsorptive disease, a neoplasm should be suspected and an imaging workup that includes the brain is warranted, with particular attention to the anterior cranial fossa. Additionally, because there are some overlapping histological features between PMTMCTs and hemangiopericytomas, it may be helpful to assess tumoral FGF-23 expression by reverse transcriptase polymerase chain reaction or immunohistochemical analysis in patients with oncogenic osteomalacia from an intracranial tumor diagnosed as, or resembling, hemangiopericytoma.

Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage.

OBJECT: Intracerebral hemorrhage (ICH) is the most serious bleeding complication of vitamin K antagonist (VKA) therapy, carrying a high mortality. Rapid reversal of VKA in ICH is critical. Plasma therapy, the standard of care in the US, is not optimal. The ideal prothrombin complex concentrate (PCC) containing all vitamin K-dependent factors (VKDFs) is not available in the US. Therefore, the authors developed a Trauma Coumadin Protocol (TCP) consisting of a 3-factor PCC available in the US (which contains insufficient factor VII [FVII]) with a low-dose recombinant FVIIa to rapidly reverse VKA. METHODS: Forty-six patients treated with the TCP were retrospectively analyzed. Fourteen patients had pre- and post-TCP plasma samples collected to assess their VKDF increment. Eleven patients had measurable intraparenchymal hematomas, which were evaluated for expansion. RESULTS: The mean pre- and post-TCP international normalized ratios (INRs) were 3.4 (median 2.9) and 1.0 (median 0.9), respectively. Once corrected, INR was maintained at < 1.3 during a patient's hospital stay. The pre-TCP median values of FII, FVII, FIX, and FX were 28%, 21%, 45%, and 20%, respectively; post-TCP median values increased to 144%, 417%, 102%, and 143%, respectively. Four of the 11 patients with measurable intraparenchymal hemorrhage had expansion at 24 hours after TCP. One patient probably (8 hours post-TCP) and 1 patient possibly (3 days post-TCP) had thrombotic complications. CONCLUSIONS: The TCP was very effective in rapidly reversing VKA-associated coagulopathy; however, this protocol should be used cautiously in patients at high risk for thrombosis.

Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy.

OBJECT: Neurosurgical patients often have mildly prolonged prothrombin time (PT) or international normalized ratio (INR). In the absence of liver disease this mild prolongation appears to be due to the use of very sensitive PT reagents. Therefore, the authors performed relevant coagulation factor assays to assess coagulopathy in such patients. They also compared plasma transfusion practices in their hospital before and after the study. METHODS: The authors tested 30 plasma specimens from 25 patients with an INR of 1.3-1.7 for coagulation factors II, VII, and VIII. They also evaluated plasma orders during the 5-month study period and compared them with similar poststudy periods following changes in plasma transfusion guidelines based on the study results. RESULTS: At the time of plasma orders the median INR was 1.35 (range 1.3-1.7, normal reference range 0.9-1.2) with a corresponding median PT of 13.6 seconds (range 12.8-17.6 seconds). All partial thromboplastin times were normal (median 29.0 seconds, range 19.3-33.7 seconds). The median factor VII level was 57% (range 25%-124%), whereas the hemostatic levels recommended for major surgery are 15%-25%. Factors II and VIII levels were also within the hemostatic range (median 72% and 118%, respectively). Based on these scientific data, plasma transfusion guidelines were modified and resulted in a 75%-85% reduction in plasma orders for mildly prolonged INR over the next 2 years. CONCLUSIONS: Neurosurgical patients with a mild prolongation of INR (up to 1.7) have hemostatically normal levels of important coagulation factors, and the authors recommend that plasma not be transfused to simply correct this abnormal laboratory value.

Emergency reversal of anticoagulation and antiplatelet therapies in neurosurgical patients.

Intracranial hemorrhage (ICH) is a common problem encountered by neurosurgeons. Patient outcomes are influenced by hematoma size, growth, location, and the timing of evacuation, when indicated. Patients may have abnormal coagulation due to pharmacological anticoagulation or coagulopathy due to underlying systemic disease or blood transfusions. Strategies to reestablish the integrity of the clotting cascade and platelet function assume a familiarity with these processes. As patients are increasingly treated with anticoagulants and antiplatelet agents, it is essential that the physicians who care for patients with ICH understand these pathways and recognize how they can be manipulated to restore hemostasis.

Pituitary tumors: diagnosis, management, and implications for reproduction.

Pituitary tumors are the most common intracranial neoplasms. They are commonly encountered by the gynecologist during an evaluation for galactorrhea, menstrual disturbances, or infertility. Although the majority of these tumors are benign, their impact on the endocrine and nervous system can be striking. The availability of neuroimaging techniques has allowed for more rapid diagnosis, affording earlier treatment. This review is intended to describe the common pituitary tumors seen by the gynecologist, and their impact on reproduction and fertility in the female patient.

Activity-dependent change in morphology of the glial tubular lattice of the crayfish medial giant nerve fiber.

An evaluation of electron micrographs of stimulated nerve fibers used to investigate the effect of action potential generation on the structure-function relationship between axons and its associated glial cells revealed that what was at first thought to be stimulation-induced damage to the glia was, in fact, limited to volume expansion and disaggregation of the glial tubular lattice. All other structures appeared well preserved and otherwise normal. Using a 4-point subjective scale for evaluation by two investigators, 50-Hz stimulation for 2 min was observed to cause a volume expansion and disaggregation of the tubular lattice. Quantitatively, the internal diameter of the stimulated tubular lattice increased 65% above the unstimulated control (50.96 +/- 2.09 nm and 30.81 +/- 0.87 nm, respectively, P < or = 0.001). Stimulation had its greatest effect on tubular lattice volume and organization in the adaxonal glial layer and a decreasing effect as distance from the giant axon increased. These effects are reversible since the tubular lattice diameter and degree of disaggregation preserved 10 min after the cessation of stimulation were not found to be different from their unstimulated paired controls. Axons injected with TEA, a voltage-gated potassium channel blocker, prevented stimulation-induced volume expansion and disaggregation of tubular lattice structure. These results are consistent with an active uptake of K+ with obligated water or, alternatively, hyperosmotic K+ uptake and a fixation-induced increase in water permeation. Either mechanism of K+ uptake would result in tubular lattice volume expansion and disaggregation and suggests that the tubular lattice serves a larger role than a simple trans-glial diffusion pathway.