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Biocompatibility and bioabsorption of microfibrillar collagen hemostat in experimental animals.

The effects of Microfibrillar Collagen Hemostat (MCH) and Gelfoam after surgical implantation into incision sites of the liver, kidney, and brain were studied in beagle dogs, rabbits, and beagle dogs, respectively. The results of these experimental animal studies suggest that MCH is comparable to Gelfoam with respect to biocompatibility, rate of bioassimilation, and a lack for adverse systemic effects. The brain, liver, and kidney tissues responded comparably to MCH and Gelfoam with a mild to moderate infiltration of macrophages and mononuclear cells. Most of the hemostatic compound had disappeared from the incision sites by Day 28 and completely disappeared by Day 84. The tissue degree response was interpreted as a factor in the process of bioassimilation of the two hemostatic materials. Both hemostatic compounds contributed to adhesion formation in the experimental models. The incidence of adhesions was somewhat lower for MCH than for Gelfoam, but both produced more adhesions than were found at the control sites. The adhesions were only to the adjacent structures and always localized to the surgical site. When MCH or Gelfoam is used under conditions similar to those in the present experimental study, where tissue approximation is impaired, and where growth of granulation tissue is stimulated by the physical presence of the hemostatic compound, there is the possibility for increased incidence of adhesion formation. However, when an intraperitoneal absorbable hemostatic compound is desired, the present studies in experimental animals suggest that MCH will be safe by exhibiting minimal tissue reaction.

Absorption

Intraocular hemorrhages: a hemostatic therapeutic approach.

Our knowledge of the local hemostatic factors capable of playing a role in certain intraocular hemorrhages is reviewed as a background to therapy with agents active in hemostasis. Common to hyphemas and subretinal hemorrhages are some conditions which are apt to disturb hemostasis and result in recurrent bleeding. They are: 1) Dilution of blood by aqueous humor or subretinal exudative fluid followed by the formation of hemostatic plugs which are prone to spontaneous lysis; 2) Contiguity of certain structures, such as the iris and the choroid, which are extremely rich in fibrinolytic activators favoring premature dissolution of the hemostatic plug and thereby recurrent bleeding; and 3) Presumptive high local concentration of fibrin degradation products (FDP), which have an anticoagulant action and would counteract hemostasis in the event of rebleeding. Based on these observations, the use of fibrinolytic inhibitors for the treatment of hyphema and subretinal hemorrhages seems warranted. Hemostatic mechanisms in intraocular hemorrhages and their treatment with various agents are discussed.

Antifibrinolytic Agents

Prospective evaluation of hemostatic techniques for liver injuries.

The methods of hemostasis used for liver injuries were evaluated prospectively in 637 patients treated at Detroit General Hospital during a 5-year period. Variables evaluated included severity of injury, presence or absence of bleeding, and methods of hemostasis, The liver injury was either not bleeding or was controlled by temporary pack compression during laparotomy in 325 patients: none of these patients, including the 284 in whom no hemostatic procedure was used, rebled postoperatively. Active bleeding at laparotomy was directly related to the severity of liver injury, and required some hemostatic procedure in 312 patients. The methods of hemostasis were liver sutures (244 patients), nonanatomic resection (30 patients), anatomic resection (21 patients), hepatic artery ligation (nine patients), hepatotomy with intraparenchymal vascular control (five patients), and temporary internal pack with later re-operation (three patients). Rebleeding occurred in eight of the 243 patients who survived (seven after liver sutures and one after nonanatomic resection) and four required re-operation for control of bleeding. Sixty-nine patients with active bleeding died. Death on the table in 38 patients was related primarily to uncontrolled bleeding from liver and major vessel injury. Postoperative rebleeding from the liver occurred in 14 of 31 patients who died after surgery: following initial control by liver sutures (seven patients); anatomic resection (four patients); and hepatic artery ligation (three patients). There was no apparent relationship between any hemostatic procedure and the subsequent appearance of the hepatic ischemia or parahepatic abscess. Based on this experience, the merits and detriments of individual hemostatic procedures are presented.

Hemorrhage

Morphology of the hemostatic plug in human skin wounds: transformation of the plug.

The transformation of hemostatic plugs in human skin wounds was studied in vivo after bleeding had stopped. Standardized bleeding time incisions were made on the dorsal side of the forearm of four normal male volunteers. The wounds were excised by punch biopsy 10 minutes, 30 minutes, or 2 hours after they had been made and studied by light and electron microscopy. The wounds were filled with red blood cells, and a network of fibrin strands was found in the wound, particularly near transected vessels. Polymorphonuclear leukocytes were encountered within transected vessels and at 2 hours also in the wounds and in concentric rings around the vessels up to 0.5 mm. from the wound. On top of the wounds a superficial scab, consisting of red blood cells and presumably air-dried proteins, had formed. Hemostatic plugs were found at the ends of transected blood vessels. At 10 minutes the plugs consisted of largely degranulated platelets which showed strong interdigitation. Fibrin was still absent from the center of the plugs. At 30 minutes the platelets became less densely packed, and small fibrin fibers were deposited between the platelets in large peripheral areas of the plugs. At 2 hours some of the platelets had assumed rounded shapes with few interdigitations and larger spaces between them. Areas in the plug with platelets that had lost their integrity alternated with areas where platelets still had their cytoplasmic matrix and were interdigitated. Fibrin fibers were especially demonstrable between the degenerated platelet vesicles. This occurred everywhere in small hemostatic plugs and in the periphery of larger plugs. In one individual it was also observed in the center of large hemostatic plugs. In the other individuals fibrin was present centrally as amorphous dark staining material which was fibrillar in tangential sections.

Adult

Scanning electron microscope study on hemostatic reaction. Mural thrombus after the removal of endothelium, with special references to platelet behavior, site of fibrin formation and microhemolysis.

Hemostatic reaction in the mural thrombus formation (up to 2 hrs) was examined by scanning electron microscopy after removal of the endothelium in the rabbit carotid artery by the use of a rough-surfaced needle. The endothelium was almost completely removed leaving a network of subendothelial microfilaments which sometimes appeared half embedded in the basement membrane. Platelet adhesion occurred on this subendothelial tissue in the following steps: attachment of discoid platelets, pseudopod formation and spreading. The subendothelium was thus covered by a layer of platelets in about 10 min. During adhesion they caught the microfilaments by their pseudopods and never produced hemispherical protrusions. Loose aggregates of the rounded platelets were then formed on them but they were frequently reversible, resulting in 1-2 hrs, in coverage by only one or two layers of the adhered platelets. This platelet reaction was weaker than that to collagen in case of bleeding in the previous report. Leukocyte participation in thrombus formation began at around 30 min. Fibrin strands appeared as tiny filaments which were attached exclusively to the activated platelets and later grew into thick and long fibers forming a network. Thus activated platelets seemed to be very important as the base of development of fibrin thrombus. Many erythrocytes were demonstrated to be destroyed at the mural thrombus after attaching to either the subendothelial components or activated platelets or fibrin strands and being deformed by the blood stream. This finding supports the hypothesis of microhemolysis in the hemostatic process by HELLEM (1961). This type of hemostatic reaction was proved to be caused by a slight manipulatory pressure on the arterial wall, suggesting the occurrence of thrombus formation in our daily life.

Animals

The hemostatic imbalance of plasma-exchange transfusion.

Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.

Amyotrophic Lateral Sclerosis

RADA16 as a novel hemostatic and regenerative agent in urology: European Association of Urology endourology up-to-date overview.

PURPOSE OF REVIEW: Self-assembling peptide (SAP) hydrogels represent a novel class of synthetic biomaterials with growing relevance in surgery. Among them, the ion-complementary peptide RADA16 has gained attention as an athermal, transparent, and biocompatible hemostatic agent. While its use is increasingly reported in multiple surgical specialties, evidence specific to urology remains fragmented. This review aims to summarize the physicochemical properties, mechanisms of action, and current clinical evidence for RADA16-based hydrogels, with a particular focus on urological applications. RECENT FINDINGS: RADA16 rapidly self-assembles into a transparent, extracellular-matrix-like nanofibrillar hydrogel upon exposure to physiological fluids, providing effective local hemostasis without reliance on the coagulation cascade. Preclinical and clinical data from other surgical fields demonstrate rapid bleeding control, favorable safety, and potential regenerative effects. Emerging urological evidence suggests that RADA16 is effective in managing hemorrhagic cystitis, radiation-induced hematuria, and bleeding during prostate surgery, including robot-assisted radical prostatectomy and benign prostate surgery. Beyond hemostasis, RADA16 may support wound healing and promotion of re-epithelialization. However, the current evidence base is limited by small sample sizes, lack of comparative studies, heterogeneous methodologies, and short follow-up. SUMMARY: RADA16-based hydrogels represent a promising adjunctive hemostatic option in urology, offering technical advantages such as transparency, absence of thermal injury, minimal swelling, and applicability in confined or high-risk settings. Robust prospective, comparative, and cost-effectiveness studies are required to define its definitive role in routine urological practice.

Humans

Enhancement of experimental anaerobic infections by blood, hemoglobin, and hemostatic agents.

Certain foreign materials have been demonstrated to enhance the infectivity of aerobic and anaerobic bacteria. Whole blood and other protein compounds encountered in surgical settings or trauma were tested for their effect on infectivity of nonsporeforming anaerobic bacteria. Infectious synergistic mixtures of Bacteroides fragilis plus Peptostreptococcus anaerobius and Bacteroides melaninogenicus plus Fusobacterium necrophorum were each diluted to a barely noninfectious or minimally infectious concentration (subinfective inoculum) that was injected intraperitoneally into mice alone and in combination with test proteins. Infectivity was measured by deaths from sepsis or abscess(es) within the abdominal cavity at autopsy at 1 week. Two hemostatic agents, Gelfoam powder and Avitene (final concentrations, 10 mg/ml), and crystalline hemoglobin (4 g/100 ml) each produced a marked increase (P < 0.001) in the rate of infection when mixed with a normally subinfective inoculum of either bacterial mixture. Fresh homologous mouse blood (0.25 ml) injected intraperitoneally without anticoagulant also significantly enhanced infectivity (P < 0.01) of a subinfective inoculum of B. fragilis plus P. anaerobius. These studies demonstrated the capacity of whole blood, hemoglobin, and hemostatic agents to enhance the infectivity of certain nonsporeforming anaerobic bacteria. The high concentrations of anaerobic bacteria in the gastrointestinal, female genital, and respiratory tracts produce an increased risk of human infection after surgery or trauma in these sites; the protein agents studied here may further enhance infection.

Anaerobiosis

Drug therapy reviews: clinical use of hemostatic agents.

Systemic hemostatic agents are reviewed. Among the agents discussed are vitamin K preparations (phytonadione, menadione, menadione sodium bisulfite, menadiol sodium diphosphate); and blood products (whole blood, plasma, cryoprecipitate, factor VIII concentrates, factor IX concentrates and fibrinogen concentrates). Normal and abnormal hemostasis and fibrinolysis are discussed, as is the general management of systemic hemostatic defects. Specific disorders covered are clotting factor deficiencies, hemophilia A, factor VIII inhibitors, von Willebrand disease, hemophilia B (Christmas disease), other congenital coagulation disorders, acquired deficiency of factors II, VII, IX and X, and defibrination syndrome.

Antibodies

A new topical hemostatic agent in gynecologic surgery.

Experiences with a topical hemostatic agent, microfibrillar collagen (MFC), material made from beef hide dermis are recounted. Topical hemostasis is facilitated by virtue of its fibrillar structure forming a sticky matrix for platelet aggregation. The material was used in women undergoing cervical conization to determine its absorption at hysterectomy 6 weeks later. In another group, it was used as the sole hemostatic agent at conization and compared with a control group in which conventional sutures were used. A larger group who underwent abdominal hysterectomy allowed comparison between MFC on the bladder muscularis and conventional suture ligature in terms of blood loss, operating time success of method used, and complications.

Administration, Topical

Hemostatic factors in primary hepatocellular cancer.

Detailed coagulation studies were performed in a group of 19 patients with primary hepatocellular cancer (PHC) and the results were compared statistically with the findings in 19 control subjects. Various funcitonal and immunochemical methods were employed in determining the possible presence of functional or structural coagulant protein abnormalities. The patient group was characterized by prolonged prothrombin times, partial thromboplastin times, and Reptilase times, increased levels of fibrinogen, factor VIII, and factor VIII-related antigen, moderately devreased levels of factor V, factor IX, factor X, antithrombin III, and plasminogen, and reduced levels of factor II and factor VII. Functional, immunochemical, and biochemical analysis failed to detect the presence of acquired protein abnormalities. These findings indicate that hemostatic changes in primary hepatocellular cancer are nonspecific in character. Severe alterations in the plasma levels of one or more of these hemostatic factors may occur.

Adolescent

Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies.

A prospective study of hemostatic abnormalities in 108 cancer patients was undertken at an oncology clinic in a university teaching hospital. Tests included Quick prothrombin time, activated partial thromboplastin time, thrombin time, platelet count, modified Ivy bleeding time, fibrinogen, fibrin degradation products (FDP), euglobulin lysis time, protamine sulfate test, and factor V, VII, VIII and X assays. Ninety-eight per cent of the patients had one or more abnormal coagulation tests. The commonest abnormalities were elevated fibrin degradation products and prolonged thrombin time. Thrombocytosis occurred in 57% of patients, hyperfibrinogenemia in 46%, thrombocytopenia in 11%, and non had hypofibrinogenmia. It is suggested that platelet count, fibrinogen concentration, and serum FDP assay are the most useful tests in assessing the hemostatic abnormalities in cancer patients, although thrombin time, factor V assay, and bleeding time may also be helpful. The peripheral blood smears of 53 patients were reviewed, and only one showed microangiopathic hemolytic anemia. The data illustrate that subclinical coagulopathy is relatively frequent in patients with malignancy.

Adolescent

Hemostatic and platelet kinetic studies in dengue hemorrhagic fever.

In an attempt to reveal certain aspects of the pathogenesis of the bleeding disorder in dengue hemorrhagic fever, hemostatic and platelet kinetic studies were carried out in 61 children with this disease. As has been shown by others, thrombocytopenia and hypofibrinogenemia were the two most prominent hemostatic defects constantly discovered. Increased intravascular clotting seemed to be one responsible factor, though not an outstanding one. This was evidenced by mildly and variably low factors II, V, VII, VIII, IX, X, and XII, and by mild to moderate increase of fibrin degradation products as well as low platelet counts and fibrinogen. In 11 cases platelet kinetic study revealed increased destruction as a main cause for the thrombocytopenia, most probably due to the underlying immunologic mechanism, i.e., via the immune complexes formed. Another factor was platelet dysfunction--the release of adenosine diphosphate.

Adenosine Diphosphate

The use of microfibrillar collagen hemostat for control of renal bleeding.

Microfibrillar collagen hemostat was used in 23 patients with renal injuries owing to multiple causes in an attempt to control small vessel bleeding from raw renal surface areas. Minimal complications have occurred with the use of this substance. Control of bleeding has been prompt and no late bleeding has occurred.

Animals

[Wound healing in viscera studied using a hemostatic gelatin-starch sponge of Polish manufacture].

The authors studied the reaction of liver, spleen and kidneys in rats to the implantation of Polish made hemostatic gelatin-starch sponge. The sponge under study evoked no disadvantageous tissue reactions in the case of liver; it was readily resorbed and did not inhibit the wound healing. It facilitated the healing of lienal wounds without any suturing and produced neither local nor general disadvantageous results. When dressing renal wounds, the sponge was completely resorbed within 3 weeks and the wound was completely healed. The renal wounds healed without any complications despite of a greater tissue reaction compared with that of liver and spleen.

Animals