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Biomedical subjects

D A Gabriel

Publications and source records attributed to D A Gabriel.

At least 19 recordsLinked to original sources
PubMed2002

Analyzing fibrin clot structure using a microplate reader.

Fibrin clot structure studies are often performed using optical methods. For example, the clot's fiber structure can be assessed by measuring light scattering as a function of wavelength. From these measurements, one can calculate the mass/length ratio (mu), a relative measure of fibrin thickness. Fiber thickness has important functional correlates in terms of clot stability and resistance to fibrinolysis. Typically, measurements to calculate mass/length ratios are carried out on high-end spectrophotometers. However, limitations of this instrument include the large sample volume required and the inability to read multiple samples at one time. To circumvent these limitations, a plate-reading spectrophotometer is more commonly used to monitor clot formation; increases in absorbance indicate clot formation, while decreases indicate clot lysis. However, it is unclear whether plate-reading spectrophotometers can be used to quantitatively evaluate fibrin fiber structure. In the current study, we compared spectrophotometric analysis of fibrin gels on single-sample and plate-reading spectrophotometers. Results show that a plate-reading spectrophotometer does not give accurate measurements of the fiber mass/length ratio. However, the plate-reading spectrophotometer can provide a qualitative measure of fiber structure for both purified fibrinogen and plasma. We suggest that plate-reading spectrophotometers can provide a convenient, rapid, and inexpensive means of analyzing fibrin clot structure.

Calcium↗
PubMed2001

Training-related changes in the maximal rate of torque development and EMG activity.

This study monitored the effects of a short-term elbow flexor training program on surface electromyographic (SEMG) spike activity. The experimental paradigm consisted of three test sessions separated by 2-week intervals. At the beginning of each session, participants (N=13) performed five maximal effort isometric contractions of the elbow flexors to serve as baseline. After 5 min of rest, the participants then engaged in a 30-trial isometric fatigue protocol during which maximal elbow flexion torque was measured with a load-cell, and the maximal rate of change in the torque (dtau/dt(max)) was obtained from the differentiated torque-time curve. Bipolar electrodes were used to monitor the SEMG spike activity of the biceps brachii. Mean spike amplitude (MSA) and mean spike frequency (MSF) were calculated for the torque development and constant-torque phases of the isometric contraction, termed Segment 1 and Segment 2, respectively. Mean power frequency (MPF) was also calculated for Segment 2. The five baseline contractions of the second and third sessions were compared with those of the first session and analyzed for training-related changes. Training increased dtau/dt(max) but failed to change maximal elbow flexion torque or MSA. However, there was an increase in the MSF during the torque development phase of the contraction (Segment 1). Both MSA and MSF were greatest during the constant-torque phase of the isometric contraction (Segment 2). There was a strong linear correlation (r=0.90, P<0.05) between MSF and MPF during (Segment 2). We hypothesize that the increase in dtau/dt(max) is due to enhanced motor-unit rate-coding. The demonstrated correlation between MSF and MPF measures will allow investigators to use spike analysis to examine the frequency content of the SEMG signal under non-stationary conditions.

Biomechanical Phenomena↗
PubMed2001

The reversal of antagonists facilitates the peak rate of tension development.

OBJECTIVE: The present study was designed to test the effects of the reversal of antagonists on the peak rate of tension development (dF/dt(max)) of the elbow extensors. DESIGN: Experimental, with matched controls. SETTING: A biomechanics research laboratory. PARTICIPANTS: Twenty-six healthy women without a history of upper extremity injury or neurologic disorder, randomly assigned to experimental (n = 13) or control (n = 13) groups. INTERVENTIONS: Two groups of healthy subjects followed identical exercise protocols, except that the control group performed maximal isometric contractions of the elbow extensors and the experimental group executed a maximal isometric elbow flexion contraction immediately before a maximal elbow extension contraction. Both groups performed 5 cycles of a 2-second contraction with 22-second rest periods between agonist muscle contractions and were evaluated at 4 test sessions spaced 2 weeks apart. MAIN OUTCOME MEASURES: All measurements were done with the shoulder and elbow at 90 degrees of flexion in the sagittal plane to ensure reproducibility. A load cell was used to measure elbow extension moment and to calculate the peak rate of tension development (dF/dt(max)). Biceps and triceps brachii surface electromyographic activity was monitored concurrently. The electromyographic measures were mean spike (peak-to-peak) amplitude and mean spike frequency of the biceps and triceps brachii activity. RESULTS: Intraclass dF/dt(max) and electromyographic reliability was good (r > or = .72) in both groups. Because biceps electromyographic measures were considerably less reliable (r < or = .53), they were not included in our analysis. While dF/dt(max) increased quadratically in both groups (p <.05), the experimental group was on average 36.1Nm. s(-1) (63%) greater across sessions 2 to 4 (p <.05). In contrast, triceps electromyographic activity did not differ significantly between groups (p >.05). The means averaged across groups exhibited a quadratic increase from session 1 to session 4: 91microV or 48% for mean spike amplitude (p <.05) and 7Hz or 16% for mean spike frequency (p <.05). CONCLUSIONS: The greater dF/dt(max) for the experimental group was not associated with increased electromyographic activity. The experimental group appeared to use the biomechanic properties of the pretensioned extensor muscle-tendon complex, rather than neurologic biasing, to accomplish its power gains.

Analysis of Variance↗
PubMed2001

Location of the platelet binding site in zymogen coagulation factor IX.

The assembly of the tenase complex on the surface of the platelet is an essential step in maintaining normal hemostasis as evidenced by the serious hemorrhagic diathesis associated with either factor IX (FIX) or factor VIII deficiencies. Understanding the regions and or residues of FIX crucial for proper binding to platelets has important clinical implications. The ability of FIX to bind activated platelets in the presence of 4 mmol/l CaCl2 was examined using electrophoretic light-scattering experiments. Wild-type FIX binds to activated platelets with dissociation constant Kd = 7.9 nmol/l. Activated FIX binds to activated platelets with Kd = 2 nmol/l. Activated factor VII does not bind activated platelets at physiological concentrations. The Gla domain of FIX is important for the binding of FIX to activated platelets since a chimera with a factor VII (FVII) template and FIX Gla [FVII(FIXGla)] has Kd = 9.6 nmol/l, and a chimera with a FVII template and FIX Gla, A and the first epidermal growth factor domain (EGF1) [FVII(FIXGla,A,EGF1)] has Kd = 9.7 nmol/l, but a chimera with a FIX template and a FVII Gla [FIX(FVIIGla)] does not bind activated platelets. Altering the fifth residue of FIX from a lysine to an alanine (Lys5<--Ala) abolishes the mutant from binding to collagen but does not affect FIX binding to the activated platelet (Kd = 9.8 nmol/l). Point mutations involved with residues 4 and 5 (Gly4<--Phe and Lys5<--no residue), residue 9 (Phe9<--Ala), residue 10 (Val10<--Lys) and residues 9-11 (Phe9<--Met, Val10<--Lys, Glu11<--Lys) do not bind to activated platelets.

Binding Sites↗
PubMed2001

Neural adaptations to fatigue: implications for muscle strength and training.

PURPOSE: This paper investigates the neural mechanisms responsible for the increase in strength that occurs during serial isometric contractions. METHODS: A three-session design was used. Thirteen subjects (N = 13) were asked to perform five maximal isometric elbow extension strength trials to serve as baseline. After a 5-min rest, the subjects were administered a 30-trial fatigue protocol. This process was repeated two more times at 2-wk intervals. Elbow extension torque and surface electromyography (EMG) of the triceps and biceps brachii were monitored concurrently. The criterion measures were elbow extension torque, root-mean-square EMG amplitude, and mean power frequency (MPF). RESULTS: Intraclass reliability ranged from good to excellent. Within each experimental session, the fatigue protocol resulted in a decrease in maximal isometric elbow extension torque as well as biceps and triceps EMG amplitude and MPF (P < 0.05). However, the mean of the 30 trials and the magnitude of the linear decrease in elbow extension torque increased across the three sessions (P < 0.05). Biceps and triceps EMG amplitude increased and MPF decreased as the number of sessions increased (P < 0.05). CONCLUSIONS: These findings suggest that the fatigue protocol served as a training stimulus to down regulate motor-unit firing frequency.

Adult↗
PubMed2000

Comparison of granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells and G-CSF--stimulated bone marrow as a source of stem cells in HLA-matched sibling transplantation.

HLA-identical bone marrow or stem cell transplantation from a sibling is the preferred treatment for patients with chronic myelogenous leukemia, bone marrow failure syndromes, relapsed acute leukemia, and specific inborn errors of metabolism. Several groups have shown that granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells (PBPCs) obtained from HLA-matched siblings are effective in reconstitution of marrow function after marrow ablative conditioning therapy. To evaluate whether G-CSF treatment before bone marrow harvest leads to enhanced recovery of PBPC counts and recovery from limited graft-versus-host disease (GVHD), we assessed the outcome of a sequential cohort of patients treated identically and then given either G-CSF--mobilized PBPCs or G-CSF--stimulated bone marrow from HLA-identical siblings. We show that the time to neutrophil engraftment is identical in the 2 cohorts, whereas platelet engraftment is earlier with the use of PBPCs. The incidence of acute GVHD was decreased, and that of chronic GVHD significantly decreased, in the group receiving bone marrow. Overall survival was not different between the 2 groups. Thus, G-CSF--stimulated bone marrow offers a source of stem cells that allows for early neutrophil engraftment with a decreased risk of GVHD.

Adolescent↗
PubMed2000

CD34+ selection of hematopoietic blood cell collections and autotransplantation in lymphoma: overnight storage of cells at 4 degrees C does not affect outcome.

The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 microg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4 degrees C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+ selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). Neutrophil recovery >500 x 10(9)/l occurred a median of 11 days (range 9-16 days) in the overnight storage group compared to 10.5 days (range 9-21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7-43) days in the overnight storage group vs 13.5 (range 8-35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4 degrees C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation(2000) 25, 559-566.

Adolescent↗
PubMed2000

Practicing a maximal performance task: a cooperative strategy for muscle activity.

The effect of practice on predicting elbow flexion movement time was studied. Participants (N = 18) performed 400 elbow flexion trials to a target in the horizontal plane. The trials were distributed equally over four sessions. The goal was to decrease the movement time (MT) for the same degree of accuracy. The electromyographic (EMG) activity of the biceps and triceps brachii was monitored with standard Beckman Ag/AgCl surface electrodes. The EMG measures formed two variable sets within one prediction equation. One variable set was composed of the onset of muscle activity relative to the start of movement (motor time) and the duration of muscle activity. The other variable set consisted of the mean amplitude value of the entire burst and of the first 30 ms (Q30) of activity. As the maximal speed of limb movement increased, the duration of muscle activity (motor time and EMG duration) decreased, and the magnitude of muscle activity (MAV and Q30) increased. Most of the change in the duration of muscle activity occurred in Session 1, while the magnitude of muscle activity continued to increase until Session 3. Multiple regression analysis revealed a cooperative strategy between the magnitude and duration of muscle activity. Early in learning, participants adjusted the magnitude of muscle activity to increase limb movement speed. As practice continued, alterations in the duration of muscle activity became more important, while the magnitude changes were less involved. Late in learning, both dimensions of muscle activity were used to decrease MT. We suggest that the interplay between the magnitude and duration of muscle activity may be due to: (a) cognitive factors related to the division of attention in a motor skill, (b) an increase in the frequency of motor unit firing that affects both dimensions of muscle activity, or (c) some combination of (a) and (b).

Adult↗
PubMed1998

Applications of a hollow fiber device to monitor hemostasis.

A global assessment of hemostasis can be determined by the perfusion of unanti-coagulated whole blood through a hollow fiber at a nominal shear rate of 300 sec(-1). Once the pressure across the hollow fiber is stable, uniform holes are punched through the top and bottom of the fiber, resulting in an optically detectable leakage of blood from the hollow fiber and a pressure drop throughout the system. Changes in the shear rate and flow profile at the puncture site are sufficient to activate platelets mechanically, resulting in a platelet plug observable by electron microscopy. Fibrin is the principal component of the luminal surface adjacent to the puncture site and a prominent fibrin tail extends downstream from this site. The time from the introduction of the punch site to 90% recovery of the baseline pressure defines the in vitro bleeding time (IVBT). The rate of the pressure recovery appears to be related to the efficiency of the thrombin-mediated recruitment of additional platelets to the plug. Pressure recovery can be delayed by either platelet or thrombin inhibitors.

Biological Assay↗
PubMed1998

Alterations in fibrin detected in coronary sinus blood after heparin and coronary angiography with a nonionic contrast agent (iohexol).

Although heparin and some radiographic contrast agents inhibit coagulation, thrombi can still form in their presence. The chemical environment in which a thrombus forms affects fibrin structure that may alter the ability of the thrombus to be lysed. Therefore, we assessed changes in fibrin structure in 13 patients referred for coronary angiography. Blood was obtained from the femoral vein, femoral artery, ascending aorta, left main coronary artery (LMCA), and coronary sinus (CS) before, during, and after coronary angiography was performed with iohexol. The number of fibrin monomers per fiber cross section was determined by turbidity measurements of fibrin gels formed from plasma samples. At baseline there was no difference in the number of fibrin monomers per fiber cross section in plasma gels generated from the different sampling sites. After iohexol administration, there was a significant decrease in the number of fibrin monomers per fiber cross section at the sampling sites ranging from - 13% to -25% compared with the respective baseline values with the largest change in the LMCA CS (51+/-16 to 38+/-15, p <0.025). Transcardiac (LM - CS value) changes in the number of fibrin monomers per fiber cross section were dependent on the timing of the sample collection in the CS. In 7 patients, the CS sample was collected approximately 2 minutes after injection of contrast material and there was no transcardiac difference. When the CS sample was obtained during contrast injection (n=6) a large transcardiac change occurred (44+/-10 to 32+/-14, p=0.01). These data show transient changes in fibrin structure during coronary angiography with iohexol. The thinner fibers formed in the presence of iohexol were more resistant to fibrinolysis.

Anticoagulants↗
PubMed1998

Conformational stability of factor VIIa: biophysical studies of thermal and guanidine hydrochloride-induced denaturation.

The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity.

Acrylamide↗
PubMed1998

Effects of repetitive dynamic contractions upon electromechanical delay.

The effect of repeated maximal effort isotonic contractions on electromechanical delay was studied. Over 4 days, 17 male subjects performed 400 rapid elbow flexion trials. The kinematics and surface electromyographic (EMG) activity of the biceps brachii of these subjects were recorded. The period from the onset of the EMG until the beginning of movement was defined as the electromechanical delay. The period from the beginning of movement until the end of the EMG was defined as the second component of the contraction. Over the 4 day period there was an increase in the speed of limb movement. The mean power frequency and the duration of the EMG during the electromechanical delay did not change, while the root-mean-square amplitude increased. The duration of the EMG during the second component of the contraction remained stable. The mean power frequency and the root-mean-square amplitude of the EMG during the second component of the contraction increased with the speed of limb movement. We conclude that the faster contractions were a result of changes in motor unit recruitment during the second component of the contraction, rather than in the electromechanical delay.

Adult↗
PubMed1998

Practice effects on the timing and magnitude of antagonist activity during ballistic elbow flexion to a target.

This study examined changes in antagonist timing and magnitude in response to ballistic elbow flexion practice. Seventeen men performed 400 ballistic elbow flexion trials to a target in the horizontal plane over 4 days of testing. A potentiometer and microswitch system at the elbow axis of rotation of a manipulandum recorded angular displacement and movement onset. Surface electrodes (Beckman Ag/AgCl) monitored the triceps brachii lateral head, and the electromyographic (EMG) signals were bandpassed between 20 and 300 Hz. The antagonist EMG burst was divided in two: early low-level activity (ANT1), and the large portion of the burst which occurs near target achievement (ANT2). Movement time decreased from 178 ms on the first test day to 136 ms on the last session. As practice improved the speed of limb movement, onset of the first component (ANT1) remained unchanged, while the second component (ANT2) started earlier. The magnitude of both portions of the antagonist burst increased from the first to last test day, but the change in ANT2 relative to ANT1 was more pronounced. These findings are used to explain discrepant observations in the literature for the temporal measure.

Adaptation, Physiological↗
PubMed1997

The physical exchange of factor VIII (FVIII) between von Willebrand factor and activated platelets and the effect of the FVIII B-domain on platelet binding.

Normal hemostasis proceeds through the assembly of coagulant complexes on a lipid surface derived from activated platelets. The activation complex assembly is governed by multiple factors including the binding constants (Kd) of the coagulant factors for the lipid surface. The formation of the tenase complex requires delivery of factor VIII (FVIII) to the activated lipid surface by von Willebrand factor (vWF). Using electrophoretic quasi-elastic light scattering (ELS), we have examined the interaction of FVIII in the presence and absence of vWF with both resting and activated gel-filtered human platelets. Resting platelets do not bind FVIII. Platelets activated by thrombin, epinephrine, or SFLLRN, but not ADP or collagen, bind unactivated FVIII if vWF is not present. In the absence of vWF, unactivated FVIII binds to activated platelets with a Kd of 10.4 nM. B-domain deleted FVIII binds to activated platelets with a Kd of 5.1 nM. Thrombin -activated FVIII (FVIIIa) binds to activated platelets with a Kd of 1.7 nM. The activation of FVIII while bound to the platelet surface can be monitored as a function of time. In the presence of vWF, binding of unactivated FVIII to activated platelets was inhibited, but not the binding of FVIIIa. Displacement of bound unactivated FVIII from the platelet surface occurs when vWF is added to the FVIII-platelet complex. The binding of FVIII to activated platelets is affected by the B-domain, the state of FVIII activation, and the presence of soluble vWF and proceeds as a multistep process. FVIII binding by activated platelets is not affected by platelet gpIIb/IIIa or by platelet vWF.

Binding Sites↗
PubMed1997

Shoulder and elbow muscle activity in goal-directed arm movements.

This research examined the electromyographic (EMG) activity of shoulder and elbow muscles during reaching movements of the upper limb. Subjects performed goal-directed arm movements in the horizontal plane. Movements which varied in amplitude, speed, and direction were performed in different sections of the workspace. EMG activity was recorded from the pectoralis major, posterior deltoid, biceps brachii short head, brachioradialis, triceps brachii long head, and triceps brachii lateral head; motion recordings were obtained with an optoelectric system. The analysis focused on the magnitude and timing of opposing muscle groups at the shoulder and elbow joints. For hand movements within any given direction of the workspace direction, kinematic manipulations changed agonist and antagonist EMG magnitude and intermuscle timing in a manner consistent with previous single-joint findings. To produce reaching movements in different directions and areas of the workspace, shoulder and elbow agonist EMG magnitude increased for those hand motions which required higher angular velocities, while the timing between opposing muscle groups at each joint was invariant.

Arm↗
PubMed1997

Reversal of antagonists: effect of elbow extension strength and endurance.

OBJECTIVE: To evaluate the reversal of elbow antagonists designed to facilitate the extensors relative to agonist-only contractions of the extensors, while using a protocol previously demonstrated to result in an increase in strength through motor learning. DESIGN: Two-group convenience sample composed of healthy subjects. SETTING: Clinic research laboratory. SUBJECTS: Twenty-eight healthy women without a history of upper extremity injury or neurologic disorder. MEASUREMENTS: Elbow extension strength and endurance were measured during maximal effort isometric reversal of the elbow antagonists (experimental group) and elbow extension only (control group) resistance exercise. Biceps brachii short head (BBS), triceps brachii lateral head (TLAT), and triceps brachii long head (TLNG) electromyographic (EMG) activity was measured concurrently. RESULTS: There were no significant differences between groups for either elbow extension strength, BBS, TLAT, or TLNG EMG activity. The experimental and control groups exhibited a significant linear (p < .01) and quadratic (p < .01) increase in baseline strength of 5.2N.m (30.5%). EMG activity from each muscle group increased linearly (p < .01) across all test sessions. Similar results were observed for elbow extension strength and biceps and triceps EMG activity during fatigue testing. CONCLUSIONS: The reversal of antagonists technique was not superior to agonist-only resistance exercise, nor did it interfere with the acquisition of muscular strength or endurance through motor learning.

Adult↗
PubMed1997

Differences between contrast media in the inhibition of platelet activation by specific platelet agonists.

RATIONALE AND OBJECTIVES: The authors evaluated the ability of three x-ray contrast agents--a nonionic monomeric agent (iohexol), a nonionic dimeric agent (iodixanol), and an ionic dimeric agent (ioxaglate)--to either directly activate platelets or inhibit a platelet agonist from activating platelets. METHODS: Fluorescence spectroscopy was used to detect the effect of contrast media on platelet activation. In this method, the platelet is first exposed to a fluorescent probe, which is de-esterified and trapped to Fluo-3 within the platelet. In the presence of calcium, the fluorescence emission from Fluo-3 is increased 80-fold. Thus, the increase in the free platelet calcium associated with platelet activation can be used to indicate platelet activation. RESULTS: None of the agents were shown to directly activate platelets. However, wide differences in the ability of contrast media to inhibit platelet activation by a specific agonist were observed. Activation of platelets by epinephrine or arachidonic acid was not affected by any of the three contrast media studied. All three agents partially inhibited collagen activation of platelets, with ioxaglate the more potent inhibitor. Ioxaglate was the only agent to inhibit thrombin activation of platelets. Inhibition of adenosine diphosphate platelet activation was more extensive with ioxaglate than with iodixanol; iohexol produced no inhibition at all. CONCLUSION: Direct activation of platelets by contrast media was not observed. Of greater importance is the finding that ionic contrast media, but not nonionic contrast media, inhibit thrombin activation of platelets by binding to the anion-binding exosite I, thus preventing thrombin from binding to and activating the platelet.

Arachidonic Acid↗