Administration Of Epsilon-aminocaproic Acid Research Articles

Epsilon aminocaproic acid is associated with acute kidney injury after life-threatening hemorrhage in children.

Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI). We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life-threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis. Of 448 children included, median (interquartile range) age was 7 (2-15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety-three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty-seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p = .002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre-LTH, and total weight-adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0-10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis. Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients.

Local administration of epsilon-aminocaproic acid reduces post-operative blood loss from surgery for closed, Sanders III\u2013IV calcaneal fractures

PurposeTo investigate whether local administration of epsilon-aminocaproic acid (EACA) is effective and safe in reducing the post-operative blood loss in surgery for Sanders III–IV calcaneal fractures.MethodsPatients with Sanders III–IV calcaneal fractures who were hospitalized in our hospital from January 2016 to February 2021 and underwent open reduction internal fixation (ORIF) via lateral approach with an L-shaped incision were included in the current study. Eighty five patients were randomly divided into two groups, EACA group (43) and control group (42). Twenty milliliters of 5% EACA solution or normal saline was perfused into the incision of patients in EACA group and control group, respectively. The volume of post-operative drainage was investigated as the primary outcome. Post-operative blood test, coagulation test, and wound complications were analyzed as the secondary outcomes.ResultsThe volume of post-operative drainage at 24 and 48 h was 164.8 ± 51.4 ml, 18.9 ± 3.8 ml for patients in EACA group, and 373.0 ± 88.1 ml, 21.2 ± 4.4 ml for patients in the control group, respectively. EACA greatly reduced the post-operative blood loss compared to the control (normal saline). The difference between the two groups was statistically significant. No statistically significant difference was found between EACA group and control group with regard to the pre-operative, baseline characteristics. Post-operative blood test results demonstrated that haemoglobin and hematocrit were significantly higher in EACA compared to those of control group. No significant difference was found between EACA group and control group in terms of the platelet counts, prothrombin time (P.T.), activated partial prothrombin time (APTT), and wound complications.ConclusionLocal administration of EACA is effective in post-operative blood loss reduction in ORIF surgeries for Sanders III–IV types of calcaneal fractures without increasing the incidence of periwound complication.

Pre-administration of a carboxypeptidase inhibitor enhances tPA-induced thrombolysis in mouse microthrombi: Evidence from intravital imaging analysis

IntroductionThrombolysis using recombinant tissue-type plasminogen activator (rt-PA) is the pharmacological treatment of choice in acute thrombotic events. However, a narrow therapeutic window and bleeding complications limit its use. We describe the role of carboxypeptidase inhibitor from potato tuber (PTCI), an inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa), on Glu-plasminogen accumulation and microthrombus dynamics in vivo and demonstrate its influence on rt-PA-mediated thrombolysis. Materials and methodsIn conjunction with real-time intravital two-photon excitation fluorescence microscopy, we produced and imaged laser-induced microthrombi in the mesenteric venules of Green Fluorescent Protein (GFP)-expressing mice. We examined microthrombus dynamics and thrombolysis patterns in vivo by measuring the changes in the fluorescence intensity of labeled Glu-plasminogen following administration of epsilon aminocaproic acid (EACA), PTCI, and rt-PA. ResultsPTCI enhanced Glu-plasminogen accumulation at the core of the thrombus by inhibiting TAFIa, while EACA inhibited this process. Exogenous rt-PA effectively triggered Glu-plasminogen activation within the thrombus and promoted thrombolysis. Administration of PTCI and rt-PA together showed no significant benefit on thrombolysis compared to rt-PA administration alone. However, early-phase systemic administration of PTCI before thrombolytic therapy by rt-PA expedited clot lysis as evidenced by significantly faster time to reach peak Glu-plasminogen fluorescence intensity and shorter time to achieve near-complete clot lysis (P = 0.014 and P = 0.003, respectively). ConclusionsPTCI potentiates rt-PA-mediated thrombolysis when administered early in acute thrombotic events. Further studies are warranted to explore the potential of TAFI inhibitors as adjunct agents in thrombolysis or thromboprophylaxis.

Safety and efficacy of epsilon aminocaproic acid (EACA) as an antihemorrhagic drug in bilateral one stage total knee arthroplasty: A double-blind randomized controlled trial

BackgroundAntifibrinolytic drugs are widely used to minimize blood loss and transfusion requirements in total knee arthroplasty (TKA). Although tranexamic acid (TXA) has been widely studied for its use in TKA, there are limited studies on epsilon-aminocaproic acid (EACA). MethodsIn a double-blind randomized control trial, all patients (n = 91) operated with bilateral simultaneous TKA were randomly given either intravenous EACA or placebo (normal saline). A single surgeon performed the TKA with posterior-stabilized implants under tourniquet. A suction drain was placed and kept for 48 h postoperatively. The intraoperative blood loss and drain output were calculated. The postoperative hemoglobin (Hb), drop in Hb, total blood loss, and number of blood transfusions in each group were calculated. ResultsBoth of the groups were comparable in terms of age, sex, body mass index, and pre-operative Hb. There was a significant difference between the EACA group and control group in terms of intraoperative blood loss (150 ml vs. 165 ml, P = 0.01), drain output (494 ml vs. 1062 ml, P < 0.001), postoperative Hb (9.9 g/dl vs. 8.6 g/dl, P = 0.002), drop in Hb (2.2 g/dl vs. 3.1 g/dl, P = 0.026) and transfusion rate (median transfusion 0 vs. 1, P < 0.001). The total blood loss, as calculated by the Hb balance method, was significantly less (P < 0.001) in the EACA group (0.99 l) compared with the control group (2.71 l). None of the patients developed any adverse reaction/complication to the drug. ConclusionIntraoperative administration of EACA significantly decreased the blood loss and postoperative transfusion rates compared with no antifibrinolytic therapy in bilateral simultaneous TKA.

The Effect of Epsilon-Aminocaproic Acid on the Development of Shunt-Dependent Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage: a Case-Control Study

The use of epsilon-aminocaproic acid (EACA) and other anti-fibrinolytic agents has been explored to prevent re-hemorrhage following subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture. One reported complication includes increased rates of hydrocephalus (HCP) due to EACA administration. Herein, we present a single-institution case-control study investigating the relationship between EACA administration and the development of shunt-dependent HCP. All patients were managed by a single neurosurgeon at the University of Alabama at Birmingham (UAB) Medical Center who treated SAH patients with EACA. A power analysis was performed to determine the sample size, and 57 patients who required a ventriculoperitoneal shunt (VPS) for management of obstructive hydrocephalus after failing an external ventricular drain wean protocol were selected. Control patients with initial obstructive hydrocephalus who did not require VPS were matched by demographic factors. The overall rate of VPS placement was 44%; the odds ratio of VPS placement after treatment with EACA was 0.63. The presence of intraventricular hemorrhage or a poor clinical exam on presentation was closely associated with eventual placement of a VPS, with the odds ratio for a Fisher CT grade 4 hemorrhage being 13.89 and a clinical exam corresponding to a Hunt and Hess score of III and IV being 17.18 and 11.00, respectively. The administration of EACA does not appear to increase the incidence of shunt-dependent HCP following SAH and may therefore be employed if clinically needed. Intraventricular hemorrhage or a poor clinical exam on presentation does appear to increase the incidence of shunt-dependent HCP following SAH.

Intra-alveolar epsilon-aminocaproic acid for the control of post-extraction bleeding in anticoagulated patients: randomized clinical trial

The aim of this study was to compare the effectiveness of the intra-alveolar administration of epsilon-aminocaproic acid (EACA) and daily gentle rinsing with EACA mouthwash with that of routine postoperative procedures for the control of bleeding after tooth extraction in anticoagulated patients. A randomized clinical trial was conducted involving 52 patients submitted to 140 tooth extractions, assigned randomly to two groups. The intervention group was treated with intra-alveolar administration of EACA immediately after surgery and gentle rinsing with EACA mouthwash during the postoperative period. The control group received routine postoperative recommendations. A single episode of immediate bleeding occurred in the intervention group. Late bleeding episodes occurred in 23 procedures (16.4%): 11 (15.7%) in the intervention group and 12 (17.1%) in the control group. Among the patients with late bleeding, 18 (78.3%) events were classified as moderate and were controlled by the patient applying pressure to a gauze pack placed over the extraction socket. The remaining five cases (21.7%) required re-intervention. No statistically significant difference in the frequency of postoperative bleeding was observed between the groups. Thus, routine measures were as effective for the control of bleeding after simple tooth extractions in anticoagulated patients as the topical administration of EACA.

Epsilon Aminocaproic Acid to Reduce Blood Loss and Transfusion After Total Hip and Total Knee Arthroplasty

BackgroundTotal hip and knee arthroplasty (THA and TKA) are associated with significant blood loss and some patients require postoperative blood transfusion. While tranexamic acid has been studied extensively among this population, we tested the hypothesis that epsilon aminocaproic acid (EACA) can reduce blood loss and transfusion after joint arthroplasty. MethodsIn April 2014, our Veterans Affairs Medical Center introduced a protocol to administer EACA during THA and TKA. No antifibrinolytics were used previously. We retrospectively compared blood loss and incidence of transfusion among patients who underwent primary arthroplasty in the year before standardized administration of EACA with patients having the same procedures the following year. Blood loss was measured as delta hemoglobin (preoperative hemoglobin − hemoglobin on postoperative day 1). All patients undergoing primary THA or TKA were included. Patients having revision surgery were excluded. ResultsWe identified 185 primary arthroplasty patients from the year before and 184 from the year after introducing the EACA protocol. There were no changes in surgical technique or attending surgeons during this period. Delta hemoglobin was significantly lower in the EACA group (2.7 ± 0.8 mg/dL) compared to the control group (3.4 ± 1.1 mg/dL) (P < .0001). The incidence of blood transfusion was also significantly lower in the EACA group (2.7%) compared to the control group (25.4%) (P < .0001). There was no difference in venous thromboembolic complications between groups. ConclusionWe demonstrated reductions in hemoglobin loss and transfusion following introduction of the EACA protocol in patients undergoing primary arthroplasty. EACA offers a lower cost alternative to TXA for reducing blood loss and transfusion in this population.

Epsilon Aminocaproic Acid for the Prevention of Delayed Postoperative Bleeding in Retired Racing Greyhounds Undergoing Gonadectomy

To evaluate the effects of epsilon aminocaproic acid (EACA) on the prevalence of postoperative bleeding in retired racing Greyhounds (RRG), and to assess its effects on selected thrombelastography (TEG) and fibrinolysis variables. Double-blinded, prospective, randomized study. 100 RRG had elective ovariohysterectomy or orchiectomy and were administered EACA or placebo for 3 days after surgery. TEG variables were analyzed preoperatively and 24, 48, and 72 hours after surgery. Thirty percent (15/50) of RRG in the placebo group had delayed postoperative bleeding starting 36-48 hours after surgery compared with 10% (5/50) in the EACA group (P = .012). On the TEG variables, the slopes for R and K time were significantly different between treatment groups (P <.05); the R and K time decreased over time in the EACA group after surgery whereas they increased in the placebo group. The angle, maximal amplitude (MA), and G slopes were also significantly different between treatment groups (P = .001, .001, and .006, respectively). The angle, MA, and G increased postoperatively over time in the EACA group and decreased in the placebo group. All these changes are supportive of hypercoagulability associated with EACA administration. Postoperative administration of EACA significantly decreased the prevalence of postoperative bleeding in RRG undergoing surgery by increasing the clot strength.

Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racingGreyhounds with appendicular bone tumors: 46 cases (2003–2008)

To determine the frequency of delayed postoperative bleeding in retired racing Greyhounds with appendicular bone tumors undergoing limb amputations. To identify if administration of epsilon-aminocaproic acid (EACA) was effective on the prevention of postoperative bleeding. Retrospective study from December 2003 to December 2008. Veterinary university teaching hospital. Forty-six retired racing Greyhounds (RRGs) diagnosed with primary appendicular bone tumors that underwent limb amputation were included in the study. None. Thirteen of 46 RRGs (28%) included in the study had delayed postoperative bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous, subcutaneous, and external bleeding that extended from the area of the surgical site that became widespread within hours, and that required administration of blood components. A paired t-test suggests that there was a significant decrease in PCV postoperatively for both dogs that bled and dogs that did not bleed (P < 0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA or both, for the prevention of postoperative bleeding. A logistic regression model determined that dogs that did not receive EACA were 5.7 times more likely to bleed than dogs that did receive EACA, when controlling for whether or not they received FFP (95% CI: 1.02-32.15, P = 0.047). This retrospective study suggests that preemptive postoperative administration of EACA appears to be efficacious in decreasing the frequency of bleeding in RRGs undergoing limb amputation; however, a prospective study is warranted to corroborate its effectiveness.

Platelet-mediated thrombolysis in patients with δ-storage pool deficiency

We present the first thrombelastographic descriptions of three patients with δ-storage pool deficiency, a platelet disorder that involves a deficiency of dense granules and moderate bleeding. The patients demonstrated a 49-54% loss of platelet-mediated clot strength over a 1-2-h period after normal thrombus formation. This pattern persisted, with some attenuation of loss of strength following administration of epsilon aminocaproic acid, desmopressin and platelets for tonsillectomy. Assessment of platelet function in patients with platelet granule disorders can be accomplished with thrombelastographic methods in ambulatory and perioperative settings; however, the effects of therapy for this disorder cannot be monitored with thrombelastography without obtaining a blood sample prior to prophylactic hemostatic intervention.

Short-Term Antifibrinolytic Therapy Before Early Aneurysm Treatment in Subarachnoid Hemorrhage: Effects on Rehemorrhage, Cerebral Ischemia, and Hydrocephalus

Long-term administration of the antifibrinolytic agent epsilon aminocaproic acid (EACA) reduces the rate of rehemorrhage in patients with aneurysmal subarachnoid hemorrhage (SAH), but is associated with cerebral ischemia. To evaluate short-term administration of EACA before early surgery in patients with SAH. Retrospective review of 356 patients admitted between June 2002 and December 2007 with a diagnosis of aneurysmal SAH. Medical records were reviewed to determine SAH risk factors, clinical grade at the time of admission, and incidence of rehemorrhage, permanent new-onset focal neurological deficits, computed tomography evidence of cerebral infarction, symptomatic vasospasm, and hydrocephalus. Patients underwent treatment of the ruptured aneurysm an average of 47.4 hours after admission and received an average total dose of 40.6 g of EACA. The mean length of time of administration of EACA was 35.6 hours. There was a total of 5 rehemorrhages, for an overall rebleeding rate of 1.4% and a rate of rehemorrhage per 24-hour period of 0.71%. Overall, the rates of symptomatic vasospasm and permanent neurological deficits attributable to ischemic stroke were 11.5% and 7.2%, respectively, and the incidence of shunt-dependent hydrocephalus was 42.3%. Patients who were treated with coiling had higher rates of symptomatic vasospasm and ischemic complications than patients who had surgery. Short-term administration of EACA is associated with rates of rehemorrhage, ischemic stroke, and symptomatic vasospasm that compare favorably with historical controls. The rate of hydrocephalus is relatively high and may be attributable to EACA treatment.

Preliminary Experience With Epsilon Aminocaproic Acid for Treatment of Intractable Upper Tract Hematuria in Children With Hematological Disorders

Gross, intractable hematuria is rare in children. Although the role of epsilon aminocaproic acid in the management of refractory hematuria is well established in the adult population, few data exist about its use in children for this indication. We present our initial experience with epsilon aminocaproic acid for the treatment of intractable hematuria after more conservative measures failed, and propose an algorithm for administration of epsilon aminocaproic acid in children. We reviewed the charts of all patients treated with epsilon aminocaproic acid for intractable gross hematuria at our institution during a period of 36 months. All patients underwent hematological evaluation and any underlying bleeding dyscrasias were addressed. All patients also underwent renal and bladder ultrasound, retrograde pyelogram and ureteroscopy. Demographic information, medical and surgical histories, and epsilon aminocaproic acid dosing and outcomes were recorded. Three boys and 1 girl 11 to 17 years old were treated with epsilon aminocaproic acid. Three patients had sickle trait (1 with nutcracker phenomenon) and 1 had hemophilia A. Three patients required packed red blood cell transfusions to maintain hematocrit. Three renal angiograms were performed, all of which were nondiagnostic. Duration of hematuria ranged from 1 to 52 weeks before administration of epsilon aminocaproic acid. Endoscopic evaluation demonstrated hematuria localized to 1 ureteral orifice in all 4 patients. All patients received 100 mg/kg epsilon aminocaproic acid orally every 6 hours, which uniformly led to cessation of hematuria. Epsilon aminocaproic acid is useful for the management of gross refractory hematuria when more conservative measures fail. Because of its potential side effects, it should be used cautiously.

Acute promyelocytic leukaemia and acquired alpha-2-plasmin inhibitor deficiency: a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30 patients.

Bleeding diathesis and a hyper-fibrinolytic state often accompany a diagnosis of Acute Promyelocytic Leukaemia (APML). This complication can have grave effects if not successfully treated, with a 10-20% incidence of haemorrhagic death. We hypothesized that alpha-2-antiplasmin levels would correlate with the risk for bleeding, and that administration of epsilon-aminocaproic acid (EACA) would attenuate that risk. To assess this, we conducted a retrospective chart review analyzing 30 APML patients, 17 of whom were treated with EACA. Thirty patients were treated, 21 with primary induction therapy. Patients with low alpha-2-antiplasmin levels were treated with a coagulopathy protocol consisting of low-dose heparin, EACA and blood product support. Seventeen patients (57%) developed haemorrhagic complications during their treatment. The presence and grade of haemorrhage appeared to be associated with the alpha-2-antiplasmin level. There were no grade IV haemorrhages or episodes of haemorrhagic death. One episode of central venous catheter associated thromboembolism and three deaths from infection during chemotherapy were observed. alpha-2-Antiplasmin levels are a reliable surrogate for fibrinolysis and haemorrhagic risk in patients with APML. Treatment with EACA is a rational way to pharmacologically inhibit fibrinolysis, is associated with a low incidence of severe haemorrhagic events, and appears to be safe with a low risk of thrombosis. Randomized clinical trials further assessing the efficacy and potential toxicity of EACA in inhibiting fibrinolysis in patients with APML are needed.

Renal complications of sickle cell disease: managing for optimal outcomes.

A broad spectrum of renal changes is observed in patients with sickle cell anemia, and ideal therapeutic measures for the management of these alterations are still being studied. Affected patients have deficient urinary concentration and potassium excretion. Perhaps owing to a compensatory mechanism, the proximal tubules are in a condition of "hyperfunction", with increased sodium and phosphorus reabsorption and greater creatinine and uric acid secretion. Mild tubular acidosis may be present. No treatment has been reported for these tubular changes, except for care in the maintenance of hydration. The use of anti-inflammatory drugs is being studied in order to inhibit the prostaglandins involved in the process. Increased renal blood flow, glomerular filtration rate, and filtration fraction are frequent findings. Hematuria commonly occurs as a consequence of red blood cell sickling in the renal medulla, papillary necrosis, or even renal medullary carcinoma. Measures such as increased fluid ingestion, urine alkalinization and, if necessary, administration of epsilon-aminocaproic acid and certain invasive procedures have been proposed to treat hematuria. Nephropathy in patients with sickle cell anemia can be manifested by proteinuria and, more rarely, nephrotic syndrome. Drugs such as prednisone and cyclophosphamide are ineffective for the treatment of patients with nephrotic syndrome. Angiotensin converting enzyme inhibitors decrease proteinuria, but their long-term effect in preventing the progression of glomerular disease has not been established. Chronic renal failure, although infrequent, may be one of the manifestations of this disease. Hemodialysis and transplantation are satisfactory therapeutic options for patients with end-stage renal disease.

Topical aminocaproic acid facilitates reepithelialization of persistent epithelial defects

Purpose. After corneal injury, persistent epithelial defects (PED’s) may occur due to the chronic failure of the regenerating epithelium to adhere to the underlying stroma. The aim of this study was to examine the potential of epsilon-aminocaproic acid (EACA) as a topical treatment for PED’s. EACA inhibits the activation of plasmin, which metabolizes fibronectin. Fibronectin, a glycoprotein, anchors corneal epithelium to the basement membrane and the underlying stroma. Methods. In anesthetized rabbits, PED’s were induced with sodium hydroxide (1 N). Seven days later, during the late healing phase, treatment began with administration of EACA (30%) to the right eye and administration of vehicle alone to the left eye three times daily. A control group received neither EACA nor vehicle. Rabbits were treated for 19 days. PED’s were visualized by fluorescein staining. Their size was mapped using digital planimetry. Results. After 11 days of treatment with EACA, treated PED’s were 50% smaller than in corneas treated with vehicle alone. Following treatment for 15 days, corneas treated with EACA had significantly greater re-epithelialization than vehicle-treated or control corneas. Frozen sections stained immunofluorescently for fibronectin appeared to qualitatively contain more adherent fibronectin in treated corneas. Transmission and scanning electron microscopy indicated that the epithelium was more polymorphic, thinner and vacuolated in untreated controls compared to EACA treated eyes. Light microscopy demonstrated more continuous adherent epithelium after EACA treatment. Conclusions. Topically administered EACA decreases both the severity and incidence of persistent epithelial defects produced by alkali burns to the cornea. EACA appears to promote adherence of the regenerating epithelium to the underlying stroma. Thus, topically administered EACA may be an effective treatment for this chronic condition.

Effect of antiproteolytic drugs: epsilon-aminocaproic acid (EACA) and aprotinin on experimental anti-GBM nephritis

Given the evidence accrued by other authors on beneficial effect of protease inhibitors on experimental immune nephritis, and following our preliminary report on abrogation of immune glomerulopathy in the rat by antifibrinolytic and antiproteolytic drug, epsilon-aminocaproic acid (EACA), we investigated the effect of this drug on the rat autologous anti-GBM nephritis. Along with the EACA we evaluated another protease inhibitor, aprotinin, an antagonist of serine proteases. EACA (0.3g/kg) or aprotinin (5000 kallkrein inhibition units, KIU/kg) was administered intraperitoneally (t.i.d.) from day 0 (preventive protocol) or day 3 (therapeutic protocol) of autologous anti-GBM nephritis induced in Wistar rats. Proteinuria, creatinine clearance and renal histopathology were assessed as markers of disease activity, while glomerular fibrin deposits (immunoperoxidase staining) and standard parameters of coagulation/fibrinolysis of peripheral blood enabled insight into local and systemic haemostatic mechanisms. Glomerular binding of anti-GBM antibodies (immunofluorescence) and serum titres of autologus nephrotoxic antibodies (haemagglutination assay) represented conditions of immune induction of glomerulopathy. Our experiments indicated that EACA, and to a lesser extent also aprotinin, are capable of preventing proteinuria (EACA, reduction by 57.6%; aprotinin, reduction by 26.8%, compared to untreated nephritic rats, day 3 post-induction) and glomerular histopathological changes, without affecting endogenous creatinine clearance, otherwise depressed in this model of glomerulonephritis. More importantly, both drugs significantly ameliorated glomerular lesions and proteinuria, even when the treatment was initiated on day 3 post-induction, after the injury has begun (EACA reduced proteinuria by 32.0%, and aprotinin reduced it by 20.9% day 7). Administration of EACA and aprotinin at doses reducing glomerular injury did not cause appreciable fibrin deposition in glomeruli of nephritic rats, nor did it modify parameters of systemic coagulation and fibrinolysis in these animals, EACA and aprotinin did not interfere with serum titres of nephrotoxic antibody, nor with the intensity of its binding to the glomerular basement membrane in vivo. Antiproteolytic drugs utilized in our studies exert their beneficial effect on autologous anti-GBM nephritis through interference with inflammatory phase of the disease, while sparing its immune induction and mechanisms of coagulation/fibrinolysis.

Safe and Effective, Prolonged Administration of Epsilon Aminocaproic Acid in Bleeding from the Urinary Tract

A total of 9 patients with macroscopic hematuria from various causes, none with evidence of disseminated intravascular coagulation, received low oral, divided doses (approximately 150mg. per kg. per day) of epsilon aminocaproic acid for up to 21 consecutive days. The hematuria was controlled effectively without overt clinical reactions. Parameters of hepatic and renal function, indicators of muscular damage, were studied in detail in 3 patients. No significant abnormalities were found.The use of small doses of epsilon aminocaproic acid was not accompanied by significant complications and appeared to be effective in special situations for the control of urinary bleeding. This therapy may have indications in a number of urological states accompanied by excessive hematuria.

A method for monitoring antifibrinolytic therapy in patients with ruptured intracranial aneurysms.

A rapid fluorometric assay technique has been utilized to assess the degree of fibrinolytic inhibition in 20 patients with ruptured intracranial aneurysms treated with epsilon-aminocaproic acid (EACA). This method quantitates the available plasminogen activity (APA) of plasma, and has proven to be a reliable means of monitoring antifibrinolytic therapy. Determination of the plasma APA also permits correlation of the level of fibrinolytic activity with putative complications of EACA therapy. Normal control plasma APA was 3.1 +/- 0.7 CTA units/ml, but in patients with subarachnoid hemorrhage (SAH), pretreatment fibrinolytic activity was supranormal at 3.78 +/- 0.88 CTA units/ml. During continuous intravenous administration of EACA (1.5 gm/hr) in patients with SAH, the plasma fibrinolytic activity was decreased to 0.9 +/- 0.31 CTA units/ml. A case described which examplifies the use of this assay. In addition, an approach to monitoring antifibrinolytic therapy using the plasma APA is proposed.

Inhibition of cold insolubility of serum cryoglobulin by Epsilon aminocaproic acid

Cold-induced insolubility of serum cryoglobulins can be inhibited by various carbohydrates and aminocarboxylic acids. Among the inhibitors, Epsilon amino caproic acid (EACA) was found to be effective at therapeutic levels in a patient who had mixed-type cryoglobulinemia. In vivo administration of EACA completely prevented cryoprecipitation; the inhibition being accompanied by a parallel decrease in the viscosity of the precooled serum. The data along with kinetics of serum EACA levels suggest specific binding of the drug to the cryoglobulins in this patient. This binding may be the basis for the observed inhibitory activity. The in vivo use of specific inhibitors of cryoglobulin precipitation may prove to have therapeutic application in the management of cryoglobulinemic patients.

Current Clotting Concepts in Urology

A modern outline of the physiology of coagulation, a simple approach to the use of laboratory investigation for patients with possible clotting disorders in unexplained hematuria and several illustrative cases are presented. The diagnosis and management of localized fibrinolysis in the genitourinary tract and intravascular coagulation as possible causes of post-prostatectomy hemorrhage are discussed. A minimum of a platelet count, fibrinogen assay and, if possible, measurement of fibrinogen-related antigens should be obtained before administration of epsilon aminocaproic acid.