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Successful hemostasis during a major orthopedic operation by using recombinant activated factor VII in a patient with severe hemophilia A and a potent inhibitor.

The treatment of bleeding episodes and the provision of perioperative hemostasis in patients with hemophilia in whom coagulation factor inhibitors have developed are a major therapeutic challenge because ordinary replacement therapy is usually ineffective. Herein we report the use of recombinant activated factor VII (rFVIIa) in providing successful hemostasis in a patient with hemophilia A and a high-titer inhibitor to factor VIII during a major orthopedic operation. rFVIIa (102 micrograms/kg) was administered intravenously every 2 to 3 hours for a total of 9 days. No excessive bleeding occurred intraoperatively or postoperatively, and no adverse effects attributable to rFVIIa were observed. This surgical procedure probably represented a greater hemostatic challenge than any previously reported operation in which rFVIIa was used. Thus, this article adds considerably to the growing body of literature that suggests the safety and efficacy of rFVIIa in providing perioperative hemostasis and treating severe bleeding episodes in patients with hemophilia and inhibitors refractory to other treatment modalities.

Adolescent↗

Superiority of electrocautery over the suture method for achieving cervical cone bed hemostasis.

OBJECTIVE: To compare the efficacy of electrocautery with that of the suture method for achieving hemostasis of the cervical cone bed. METHODS: We performed a retrospective chart review of all patients who underwent cold-knife conization of the cervix over a 5-year period. Patients were categorized into two groups: the cautery group, in which the cone bed was electrocauterized with a hand-held electrocoagulation device; and the suture group, in which hemostasis was achieved by a continuous locking suture placed circumferentially around the cone bed. Outcome measures evaluated include estimated blood loss, operative time, and incidence of complications, including secondary hemorrhage, cervicitis, and cervical stenosis. Data were analyzed by Student t test, chi(2) test, linear regression, and multiple logistic regression where appropriate. RESULTS: There were 156 women in the cautery group and 35 in the suture group. The cautery group had significantly lower estimated blood loss (27 mL versus 101 mL; P <.01) and shorter operative time (34 versus 43 minutes; P <.01) than the suture group. The procedure-related complication rate was 6.4% in the cautery group, compared with 14.3% in the suture group (P = nonsignificant). A higher use of lateral sutures, vasopressors, and thrombotic agents was seen in the cautery group. However, even after adjusting for these variables, mean estimated blood loss (33 mL, P <.01) and mean operative time (34 minutes, P <.01) were significantly less in the cautery group than in the suture group. CONCLUSIONS: Cauterization of the cone bed is superior to suture as a method of achieving hemostasis, with significantly less blood loss and shorter operative time.

Adult↗

Cornual pregnancy successfully treated laparoscopically with fibrin glue hemostasis.

BACKGROUND: Conventionally, cornual pregnancy has been treated by cornual resection or hysterectomy at laparotomy because it is usually hard to achieve hemostasis of the myometrial wound. We describe laparoscopic treatment with fibrin glue hemostasis in a woman with cornual pregnancy following salpingectomy. CASE: A 39-year-old woman who had a history of tubal pregnancy treated by salpingectomy presented with abdominal pain 6 weeks after her last menstrual period. Clinical and laparoscopic findings established a diagnosis of right cornual pregnancy. The products of gestation were removed laparoscopically, and the bleeding area of myometrium was first coagulated using bipolar forceps and then sealed by fibrin glue. CONCLUSION: Laparoscopy appears to be a safe alternative for patients with early cornual pregnancy, and fibrin glue is useful for achieving hemostasis of oozing myometrial wounds.

Adult↗

Hemostasis of punctured vessels using Doppler-guided high-intensity ultrasound.

The use of Doppler ultrasound was investigated to determine if it would aid in guiding the application of high-intensity focused ultrasound (HIFU) to stop bleeding from punctured vessels. Major vessels (abdominal aorta, illiac, carotid, common femoral and superficial femoral arteries and the jugular vein) were surgically exposed, punctured and treated in anesthetized pigs. Treatment was applied when the Doppler sounds indicated the focus coincided with the bleeding site. In 89 treatment trials, the average time to achieve major hemostasis (a point where bleeding was reduced to a level of only oozing) was 8 s, and for complete hemostasis was 13 s. These times were significantly shorter than those of an identical former study in which only visual guidance was used. In that study, the average times for major and complete hemostasis were 40 and 62 s, respectively. The advantage of Doppler guidance in applying HIFU in treating bleeding vessels was demonstrated.

Animals↗

Monitoring anticoagulation and hemostasis in cardiac surgery.

The need to monitor anticoagulation and hemostasis during and after cardiac surgery has led to recognition of the importance of evaluation and use of hemostasis monitors in this setting. Consequently, rapid and accurate identification of abnormal hemostasis has been the major impetus for the development of point-of-care tests and their use in transfusion algorithms for cardiac surgical and other critically ill patients.

Algorithms↗

Hemostasis using high intensity focused ultrasound.

High intensity focused ultrasound (HIFU) has been shown to be an effective method of hemostasis, in animal studies, for both solid organs and blood vessels. Two distinct effects of HIFU, thermal and mechanical, appear to contribute to hemostasis. Acoustic hemostasis may provide an effective method in surgery and prehospital settings for treating trauma and elective surgery patients. A review of the methodology is given.

Animals↗

Effects of diltiazem, dipyridamole, and their combination on hemostasis.

Calcium channel blockers and antiplatelet agents, alone and in combination, have been reported to induce bleeding in patients undergoing surgery. Since diltiazem and dipyridamole influence platelet function in vitro and in vivo, their influence on hemostasis was examined in five normal men given diltiazem, 90 mg by mouth, followed by 60 mg every 6 hr for 48 hr, or dipyridamole, 75 mg by mouth every 8 hr for 48 hr. At 24 hr, the alternate drug was added to the regimen to assess effects of the combination on hemostasis. Platelet aggregation, serum thromboxane B2 and 6-keto-PGF1 alpha concentrations (stable metabolites of thromboxane A2 and prostacyclin), bleeding time, prothrombin time, partial thromboplastin time, and serum diltiazem concentrations were measured. Diltiazem and dipyridamole alone and in combination had no significant effect on bleeding time, prothrombin time, or partial thromboplastin time. Platelet aggregation induced by threshold concentrations of adenosine diphosphate, epinephrine, and calcium ionophore A 23187 were inhibited by diltiazem and dipyridamole alone and in combination. The only change in prostaglandin concentrations was a slight increase in serum 6-keto-PGF1 alpha after diltiazem. Despite influences on platelet function, neither diltiazem nor dipyridamole alone or in combination induced clinically relevant changes in hemostasis.

6-Ketoprostaglandin F1 alpha↗

G13 is an essential mediator of platelet activation in hemostasis and thrombosis.

Platelet activation at sites of vascular injury is essential for primary hemostasis, but also underlies arterial thrombosis leading to myocardial infarction or stroke. Platelet activators such as adenosine diphosphate, thrombin or thromboxane A(2) (TXA(2)) activate receptors that are coupled to heterotrimeric G proteins. Activation of platelets through these receptors involves signaling through G(q), G(i) and G(z) (refs. 4-6). However, the role and relative importance of G(12) and G(13), which are activated by various platelet stimuli, are unclear. Here we show that lack of Galpha(13), but not Galpha(12), severely reduced the potency of thrombin, TXA(2) and collagen to induce platelet shape changes and aggregation in vitro. These defects were accompanied by reduced activation of RhoA and inability to form stable platelet thrombi under high shear stress ex vivo. Galpha(13) deficiency in platelets resulted in a severe defect in primary hemostasis and complete protection against arterial thrombosis in vivo. We conclude that G(13)-mediated signaling processes are required for normal hemostasis and thrombosis and may serve as a new target for antiplatelet drugs.

Animals↗

Preoperative evaluation of primary hemostasis in patients with thrombocytopenia using the Thrombostat 4000.

It is difficult to estimate the risk of hemorrhage that may follow an invasive or surgical procedure in patients with thrombocytopenia or platelet dysfunction. Conventional functional tests for the evaluation of primary hemostasis have been questioned. We have evaluated the in vitro bleeding time (IVBT) using the Thrombostat 4000 in 25 patients with thrombocytopenia in order to estimate the risk of bleeding following an invasive or surgical procedure. Using the IVBT, it was possible to suggest and evaluate preoperative treatment in order to restore primary hemostasis. All patients studied had their operations without bleeding complications. From these observations we conclude that the IVBT is a convenient and useful tool in the evaluation of primary hemostasis in these patients.

Adult↗

Endoscopic hemostasis in acute diverticular bleeding.

BACKGROUND AND STUDY AIMS: Early reports of urgent colonoscopy in acute lower intestinal bleeding suggest a role for endoscopic therapy for bleeding colonic lesions, but scant data exist on bleeding diverticula. We report our experience with endoscopic hemostasis in acute diverticular bleeding. PATIENTS AND METHODS: Bleeding diverticula were identified on urgent diagnostic endoscopy in five patients with acute gastrointestinal bleeding, two in the duodenum, and three in the colon. All patients had co-morbid conditions preventing more conventional therapeutic approaches. The five cases are described, including the technique of endoscopic hemostasis and outcome. RESULTS: Endoscopic therapy using epinephrine injection, thermal cautery and/or laser therapy successfully induced hemostasis in all patients. One patient died of co-morbid illness during the hospital stay, while the remaining four patients had no recurrent bleeding over a mean follow-up period of 20.6 months. CONCLUSION: Endoscopic therapy of bleeding diverticula is technically possible when the culprit diverticulum can be identified. This therapeutic modality may have a place in debilitated patients in whom other more invasive procedures are contraindicated, but further experience is needed to establish its safety.

Acute Disease↗

Influence of ACE inhibition on myocardial damage, the Kallikrein-Kinin system and hemostasis during cardiopulmonary bypass surgery.

BACKGROUND: ACE inhibitors may have a cardioprotective effect by enhancing bradykinin levels during cardiopulmonary bypass (CPB). However, ACE inhibition could lead to unwelcome effects on the kallikrein contact phase during CPB (since reduction of kallikrein activity by aprotinin has been shown to be beneficial) and may alter the hemostasis. We examined the effects of ACE inhibitors on intraoperative myocardial damage, kallikrein contact phase and hemostasis in patients undergoing CPB. METHODS: 47 patients randomly received either 20 mg/d enalapril or placebo. Creatine kinase (CK and CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), thrombin-antithrombin III complex (TAT), fibrinogen and kallikrein-like activity were measured before surgery, during and immediately after CPB, at the end of surgery and 1, 3 and 5 days after surgery. RESULTS: No significant differences between enalapril- and placebo- treated patients concerning CK (318 +/- 38.6 U/l vs. 316 +/- 16.8 U/l), CK-MB, LDH, TnT (1.81 +/- 0.45 ng/ml vs. 1.52 +/- 0.34 ng/ml), TAT, fibrinogen and kallikrein-like-activity could be found during study period. CONCLUSIONS: Reduction of ischemic injury during CPB is not achieved with ACE inhibitors. However, treatment of patients with ACE inhibitors before and during CPB is fully feasible without side effects affecting the kallikrein contact phase or significant influence on hemostasis.

Administration, Oral↗

Hemostasis during normal pregnancy and puerperium.

During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability, thus decreasing bleeding complications in connection with delivery. The most important initial factor for acute hemostasis at delivery is, however, uterine muscle contractions, which interrupt blood flow. Global tests such as Sonoclot signature, the Thromboelastogram, and a new method analyzing overall plasma hemostasis, all show changes representative of hypercoagulability during pregnancy. Increased endogenous thrombin generation, acquired activated protein C resistance, slightly decreased activated partial thromboplastin time (aPTT) and increased prothrombin complex level (PT) measured as international normalized ratio (INR) of less than 0.9 have been reported as well. In normal pregnancy, the platelet count is within normal range except during the third trimester when benign gestational thrombocytopenia, 80 to 150 x 10 9/L, can be observed. Platelet turnover is usually normal. Activation of platelets and release of beta-thromboglobulin and platelet factor 4 are reported. The bleeding time is unchanged during normal pregnancy. Most blood coagulation factors and fibrinogen increase during pregnancy. Factor (F) XI is the only blood coagulation factor that decreases. Blood coagulation inhibitors are mainly unchanged but the level of free protein S decreases markedly and the level of tissue factor pathway inhibitor increases. Thrombomodulin levels increase during pregnancy. Fibrinolytic capacity is diminished during pregnancy, mainly because of markedly increased levels of plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and plasminogen activator inhibitor-2 (PAI-2) from the placenta. Thrombin-activated fibrinolysis inhibitor is reported to be unaffected. The total hemostatic balance has been studied by analyses of prothrombin fragment 1+2, thrombin-antithrombin complex, fibrinopeptide A, soluble fibrin, D-dimer, and plasmin-antiplasmin complex. There is activation of blood coagulation and a simultaneous increase in fibrinolysis without signs of organ dysfunction during normal pregnancy. These changes increase as pregnancy progresses. During delivery, there is consumption of platelets and blood coagulation factors, including fibrinogen. Fibrinolysis improves and increases fast following childbirth and expulsion of the placenta, resulting in increased D-dimer levels. These changes are self-limiting at normal delivery. The hemostatic changes, noted during pregnancy, normalize after delivery within 4 to 6 weeks. Platelet count and free protein S, however, can be abnormal longer. Hemostasis should not be tested earlier than 3 months following delivery and after terminating lactation to rule out influences of pregnancy. PAI-1 and PAI-2 levels decrease fast postpartum, but PAI 2 has been detected up to 8 weeks postpartum. alpha 2 -antiplasmin, urokinase, and kallikrein inhibitor levels have been reported to be increased 6 weeks postpartum.

Biomarkers↗

Hemostasis defects associated with cardiac surgery, prosthetic devices, and other extracorporeal circuits.

This discussion has provided a review of the available literature regarding alterations of hemostasis associated with CPB surgery, the use of prosthetic devices, and apheresis. The key to prevention of CPB hemorrhage is to obtain an adequate preoperative workup. Of extreme importance is an adequate history with respect to bleeding tendencies and thrombotic tendencies in both the patient and the family; of equal importance is a careful history regarding the use of drugs affecting hemostasis, especially drugs known to interfere with platelet function. A careful physical examination, searching for clues of a real or potential bleeding diathesis, may also prevent catastrophic cases of hemorrhage. An adequate presurgical screen must be performed in surgical patients. In addition to the usual prothrombin time, partial thromboplastin time, and platelet count, a standardized template bleeding time (and thrombin time in patients subjected to CPB) should be performed. The use of these simple testing modalities will guard against significant defects in vascular and platelet function. Most instances of nontechnical surgical and cardiovascular surgical hemorrhage are due to several well-defined defects in hemostasis that should be readily controlled if approached in a logical manner as a team effort among surgeons, pathologists, and hematologists.

Arteriovenous Shunt, Surgical↗

Endoscopic hemostasis of upper gastrointestinal bleeding with histoacryl: last resort before surgery.

Five patients presented with acute upper gastrointestinal bleeding, underwent diagnostic and therapeutic endoscopy. The source of bleeding was identified in each case. Two patients had a large chronic gastric ulcer, one had a stress ulcer, one had a gastric ulcer with hypertrophic gastropathy, and one had a malignant infiltration of the second part of the duodenum. Conventional first-line therapeutic modalities failed to induce hemostasis in these bleeding lesions. Hemostasis was successfully achieved in each case using an endoscopic intralesional injection of Histoacryl. This agent may represent a last resort for endoscopic hemostasis before surgery.

Aged↗

Transcatheter arterial embolization for massive bleeding from duodenal ulcers not controlled by endoscopic hemostasis.

BACKGROUND AND STUDY AIMS: We evaluated the efficacy of transcatheter arterial embolization (TAE) in patients in whom endoscopic hemostasis of a massively bleeding duodenal ulcer failed. PATIENTS AND METHODS: TAE was performed in 11 patients with endoscopically uncontrollable massively bleeding duodenal ulcers, and the results and long-time outcome were studied. Two additional cases of failed endoscopic hemostasis were treated surgically without TAE. The entire group of 13 patients represented 5% of endoscopically treated duodenal ulcers and 0.6% of all cases with upper gastrointestinal bleeding who underwent emergency endoscopy (n = 2073). All but one of these 13 patients had concomitant disease. RESULTS: Arteriograms performed before TAE revealed extravasation of contrast material around the gastroduodenal artery (GDA), the anterior superior pancreaticoduodenal artery (ASPD), or the posterior superior pancreaticoduodenal artery (PSPD) in six of 11 cases. We failed to stop the bleeding in one patient, in whom only the common hepatic artery side of the GDA bleeding site was embolized; this patient died. TAE was successful in the other ten patients, in whom the long stretch of the GDA, including the ASPD and PSPD, was embolized around the bleeding site. Two surgically treated patients died within a week. CONCLUSIONS: Our findings indicate that TAE may induce hemostasis in 90% of patients with serious concomitant diseases who have endoscopically uncontrollable massive bleeding from duodenal ulcers.

Aged↗

Use of the PFA-100 in the assessment of primary, platelet-related hemostasis in a pediatric setting.

The platelet function analyzer, PFA-100, has been designed to provide an in vitro measure of primary hemostasis simply, quickly, quantitatively, and accurately to aid in the routine screening of patients with potential hemorrhagic risk due to abnormal platelet plug formation. The system measures the closure time (CT), or the time taken for platelets in a sample of anticoagulated blood to form a plug that occludes a microscopic aperture cut into a membrane coated with collagen and either epinephrine or ADP. The high shear stresses produced in the analyzer lead to platelet plug formation that is greatly dependent on von Willebrand's factor (vWF). In this article, we detail the system itself and describe our initial studies using the PFA-100 to assess primary hemostasis in pediatric populations. Normal ranges have been established for healthy children and neonates. CTs for healthy children are independent of the needle gauge (21G or 23G) used for blood sampling. They are similar to CTs for healthy adults, but neonates have significantly shorter CTs, likely due to increased levels of vWF. Children with hemophilia have normal CTs, whereas seven out of eight patients with von Willebrand's disease (vWD) have abnormally long CTs. CT reproducibility between duplicate samples is excellent. Our preliminary results indicate that the PFA-100 will be useful in the evaluation of primary hemostasis in children, as well as in adults.

Adolescent↗

Vascular hemostasis in flowing blood in children.

This review considers differences in hemostasis among newborns, children, and adults from the standpoint of the vascular endothelium and, where appropriate, in the presence of flowing blood. Special procoagulant features of newborn hemostasis include unusually large von Willebrand factor multimers, augmented platelet transport under flow conditions, and greater ability of newborn endothelium to generate tissue factor. Special anticoagulant features in the newborn include increased vessel wall glycosaminoglycan activity, elevated alpha2-macroglobulin, and increased percentage of free protein S. The net effect of the differences is that hemostasis is generally achieved in all age groups but is developmental in nature. In addition to congenital hypercoagulable states and catheter placement, developmental vascular anomalies appear to constitute a thrombotic risk, at least in some children (and possibly adults).

Adult↗

Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer.

With the use of the PFA-100 platelet function analyzer to evaluate primary hemostasis in whole blood, measured as closure time (CT), neonates had shorter CTs than members of an adult control group. Multivariate analysis of measures that contribute to primary hemostasis showed that higher hematocrits and increased ristocetin cofactor activity were the best correlates for CTs of cord blood. These 2 factors may also enhance primary hemostasis in vivo and compensate for the impaired platelet function of the newborn.

Adult↗