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At least 235 records · Page 13Linked to original sources
PubMed2003

Hemostatic effect of Vivostat patient-derived fibrin sealant on split-thickness skin graft donor sites.

Topical hemostatic agents are used frequently to control bleeding of skin graft donor sites. In this study, the hemostatic properties of Vivostat (Vivolution A/S, Birkerød, Denmark) patient-derived fibrin sealant were compared with a control group of spray thrombin solution, which is considered an industry standard for topical hemostasis. Treatments were applied simultaneously to two randomly chosen halves of a single split-thickness single donor site in patients in five United States surgical centers. The time to achieve satisfactory hemostasis (< or =10 min) was estimated on each half of the wound as the time at which active bleeding had stopped and the wound was suitable for application of a surgical dressing. The time to hemostasis of wounds treated with Vivostat (Vivolution A/S) patient-derived sealant was significantly shorter in comparison with wounds treated with thrombin solution (medians: Vivostat, 31 seconds; thrombin, 58 seconds; p=0.0012). No abnormalities in wound healing were reported for either treatment site 1 week after the operation. Vivostat (Vivolution A/S) sealant is a more rapidly effective topical hemostatic agent than thrombin on split-thickness skin graft donor sites.

Adult↗
PubMed2003

Comparison of 10 different hemostatic dressings in an aortic injury.

BACKGROUND: Uncontrolled hemorrhage is the leading preventable cause of death on the battlefield. Similarly, hemorrhage accounts for 80% of all deaths within the first 48 hours of injury in civilian trauma patients. New methods of hemostasis are required to reduce hemorrhagic mortality. The purpose of this study was to compare nine hemostatic dressings for their efficacy in controlling bleeding from an otherwise fatal aortic injury in a pig model. Each hemostatic dressing was compared with the current standard U.S. Army field gauze dressing for a 1-hour period. METHODS: Fifty-nine anesthetized pigs were instrumented with catheters and splenectomized. Nine test dressings (n = 5 per group) and two control groups (gauze, n = 9; suture, n = 5) were applied to a 4.4-mm aortotomy through the spraying jet of blood, and direct pressure was held for 4 minutes and then released. Survival, blood loss, and other variables were measured over a 1-hour period. RESULTS: All animals with fibrin dressing and those receiving suture repair (five of five in both groups) survived the 1-hour observation period with minimal bleeding in the postocclusion period (< 37 mL). Those in the other dressing groups exsanguinated within 10 minutes, except for two animals in the gauze group surviving 1 hour. CONCLUSION: With one 4-minute application, a single fibrin dressing stopped bleeding from an aortotomy, which was equivalent to sutured repair. No other test group exhibited any evidence of significant hemostatic efficacy.

Animals↗
PubMed2006

Making sense of the preclinical literature on advanced hemostatic products.

A number of new hemostatic products have been developed recently for use in trauma settings of severe uncontrolled bleeding. Currently, the literature on these products is controversial, with efficacy demonstrated under some circumstances but not others. In this review, we analyze the current literature pertaining to four of the most promising products (dry fibrin sealant dressing, Rapid Deployment Hemostat, HemCon chitosan dressing, and QuikClot) that have been suggested for use in combat casualty care applications. In particular, this analysis takes into account the characteristics of the animal models used for efficacy testing of these products, the desired characteristics of hemostatic dressings, and specific safety considerations. Animal models ranged from those featuring low-pressure/low-flow bleeding to those featuring high-pressure/high-flow bleeding. When data are viewed in the context of the specific characteristics of the differing animal models used, seemingly disparate experimental results related to efficacy and safety become quite complementary and lead to recommendations for the use of different products in different injury scenarios. Mission and training requirements will dictate the use of these products by military and civilian prehospital care providers.

Animals↗
PubMed2006

A special report on the chitosan-based hemostatic dressing: experience in current combat operations.

BACKGROUND: Hemorrhage remains a leading cause of death in both civilian and military trauma patients. The HemCon chitosan-based hemostatic dressing is approved by the US Food and Drug Administration (FDA) for hemorrhage control. Animal data have shown the HemCon dressing to reduce hemorrhage and improve survival. The purpose of this article is to report preliminary results of the hemostatic efficacy of the HemCon dressing used in the prehospital setting on combat casualties. METHODS: A request for case information on use of HemCon dressings in Operation Iraqi Freedom and Operation Enduring Freedom was sent to deployed Special Forces combat medics, physicians, and physician assistants. RESULTS: Sixty-eight uses of the HemCon dressing were reported and reviewed by two US Army physicians. Four of the 68 cases were determined duplicative resulting in a total of 64 combat uses. Dressings were utilized externally on the chest, groin, buttock, and abdomen in 25 cases; on extremities in 35 cases; and on neck or facial wounds in 4 cases. In 66% of cases, dressings were utilized following gauze failure and were 100% successful. In 62 (97%) of the cases, the use of the HemCon dressing resulted in cessation of bleeding or improvement in hemostasis. There were two reported dressing failures that occurred with blind application of bandages up into large cavitational injuries. Dressings were reported to be most useful on areas where tourniquets could not be applied to control bleeding. The dressings were reported to be most difficult to use in extremity injuries where they could not be placed easily onto or into the wounds. No complications or adverse events were reported. CONCLUSION: This report on the field use of the HemCon dressing by medics suggests that it is a useful hemostatic dressing for prehospital combat casualties and supports further study to confirm efficacy.

Bandages↗
PubMed1994

A study on the hemostatic effect of sodium alginate on uterocervical hemorrhage.

We examined a sodium alginate preparation (Alto) to determine its hemostatic effect, in comparison with other topical drugs, on hemorrhages in the uterocervical area. A total of 149 patients with hemorrhage from cervical erosion or after-treatment bleeding of the cervix uteri were subjects in this trial, and 84 (79%) of 106 patients treated with this preparation experienced a hemostatic effect. A significant positive correlation (p < 0.001) was noted between the degree of tissue adhesiveness and the hemostatic effect in all the drugs tested. As for the tissue adhesiveness, Alto was significantly more favorable (p < 0.001) than both Thrombin and Francetin T powder. Because Alto was softened by tissue moisture, its topical adhesiveness could be increased, which suggested that Alto was superior in hemostasis.

Adolescent↗
PubMed2004

A novel digital tourniquet using a sterile glove and hemostat.

BACKGROUND: Surgery of the digit is facilitated with adequate hemostasis for visualization of the operative field. Several types of tourniquets have been used for this purpose, including glove fingers, Penrose drains, Marmed digital tourniquets, and standard pneumatic tourniquets. OBJECTIVE: To present a novel method to achieve hemostasis during surgery of the digit. MATERIALS: A slightly oversized sterile glove, a hemostat, and a pair of scissors. CONCLUSION: We present a novel method to achieve hemostasis using a sterile glove and a hemostat, that allows the surgeon to methodically titrate the amount of compression necessary to attain a bloodless field while minimizing the risks of excessive pressures. Surgery of the digit is facilitated with adequate hemostasis for visualization of the operative field. Several types of tourniquets have been used for this purpose, including glove fingers, Penrose drains, Marmed digital tourniquets, and standard pneumatic tourniquets. We present a novel method to achieve hemostasis using a sterile glove and a hemostat that allows the surgeon to methodically titrate the amount of compression necessary to attain a bloodless field while minimizing the risks of excessive pressures.

Fingers↗
PubMed2005

Hemostatic effects of fibrinogen gamma-chain dodecapeptide-conjugated polymerized albumin particles in vitro and in vivo.

BACKGROUND: Prototypes of platelet (PLT) substitutes have been studied and the focus was on a dodecapeptide, HHLGGAKQAGDV (H12), which is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411) and exists only in the fibrinogen domain. STUDY DESIGN AND METHODS: H12 was conjugated to the surface of polymerized albumin particles (polyAlb) as biocompatible and biodegradable particles with a mean diameter of 260 +/- 60 nm, and the hemostatic ability of H12-conjugated polyAlb (H12-polyAlb) under flow conditions and thrombocytopenic rats have been studied. RESULTS: H12-polyAlb enhanced the in vitro thrombus formation of activated PLTs on a collagen-immobilized plate when exposed to the flowing thrombocytopenic imitation blood. Furthermore, the analysis of the tail bleeding time of rats that were made thrombocytopenic by busulfan injection showed that H12-polyAlb had a hemostatic effect. Based on the bleeding time and the amount injected, the hemostatic capacity of 20 H12-polyAlb was estimated to correspond to that of one PLT. CONCLUSION: These results were important first steps toward the development of PLT substitutes and indicated that H12-polyAlb may be a suitable candidate for an alternative to human PLT concentrates transfused into thrombocytopenic patients in the future.

Albumins↗
PubMed2005

Use of fibrin glue as a hemostatic in endoscopic sinus surgery.

Endoscopic sinus surgery (ESS), especially when combined with turbinectomy and/or with submucous resection of the septum, may involve postoperative bleeding that might end with nasal packing. Nasal packing causes pain, rhinorrhea, and inconvenience and may not stop the postoperative bleeding. The aim of our study was to compare the hemostatic properties of the second-generation surgical sealant Quixil (Crosseal) with those of nasal packing in ESS. We performed a prospective randomized trial in 64 consecutive patients who underwent ESS and presented excessive intraoperative and/or postoperative bleeding. They were allocated by the sealed-envelope method into two groups. A routine ESS procedure was ended with Merocel nasal packing in group 1, and with aerosol application of Quixil sealant at the operative site in group 2. The hemostatic effects were evaluated objectively in the clinic by anterior rhinoscopy and endoscopy and assessed subjectively by the patients at follow-up visits. In group 1, various types of postoperative bleeding occurred in 25% of patients. In group 2 there was no postoperative bleeding, except for 1 case of late hemorrhage (3.12%). Drainage and ventilation of the paranasal sinuses were not impaired. There were no allergic reactions to the glue. We conclude that aerosol application of fibrin glue can be readily performed in ESS, requires no special treatment (antibiotics), and appears to have an adequate hemostatic effect. The use of this second-generation glue in ESS appears to stop nasal bleeding well and to be relatively safe and convenient.

Adolescent↗
PubMed2001

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.

OBJECTIVE: To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. DATA EXTRACTION: The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. DATA SYNTHESIS: Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. CONCLUSIONS: Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.

Aminocaproates↗
PubMedDate not supplied

Systemic hemostatic medications for reducing surgical blood loss.

OBJECTIVE: To review randomized trials involving the use of systemic hemostatic medications for reducing surgical blood loss. DATA SOURCES: Articles were obtained through searches of MEDLINE (1966-September 2000). The bibliographies of retrieved publications were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that involved medications used for systemic hemostasis in the perioperative period were included. DATA EXTRACTION: Randomized studies involving conjugated estrogens, aminocaproic acid, tranexamic acid, desmopressin, and aprotinin for systemic hemostasis were extracted. Studies of proton-pump inhibitors for upper gastrointestinal bleeding and octreotide for variceal bleeding were excluded, as were trials involving the use of any hemostatic agent for cardiovascular surgery. The primary outcome under review was a reduction in bleeding as defined by reduced transfusion requirements. DATA SYNTHESIS: There is limited efficacy and toxicity information concerning the use of conjugated estrogens for reducing surgery-related bleeding. Similarly, there are a limited number of randomized studies involving aminocaproic acid and tranexamic acid, and with the exception of tranexamic acid for reducing transfusion requirements with knee surgery, the study results are either conflicting or negative. For desmopressin, evidence from a substantial number of randomized trials documents its lack of efficacy. Aprotinin has reduced bleeding and transfusion requirements in a number of randomized studies involving patients undergoing orthopedic surgery, but cost-effectiveness studies are needed to better define its therapeutic role. Trials of aprotinin during hepatic surgery have yielded conflicting results. CONCLUSIONS: Most hemostatic medications used for reducing surgery-related bleeding have limited or contradictory evidence of efficacy.

Adult↗
PubMed2005

[Secondary bladder amyloidosis with severe recurrent hematuria: transurethral Mickuliz procedure as hemostatic option].

OBJECTIVES: Primary localized amyloidosis of the urinary bladder generally has a benign course. On the contrary, secondary amyloidosis, a consequence of systemic amyloidosis, may have massive bleeding and produce complications such as bladder rupture or life-threatening hemodynamic problems requiring desperate hemostatic procedures such as hypogastric artery embolization or ligature, or cystectomy. We report one case in which hemostasis was achieved by a Mickulicz transurethral bladder tamponage. METHODS: 58 year old female with very aggressive rheumatoid arthritis and secondary renal amyloidosis under chronic hemodialysis presenting with severe hematuria after hip replacement. An inflamed bladder was found, the biopsy of which showed edema in all layers with blood vessel walls enlarged by amiloyd deposits. After several unsuccessful transurethral hemostatic procedures, intravesical formalin irrigation was carried out together with a Mikulicz type gauze packaging after urethral dilation. The gauze was withdrawn three days later without bleeding recurrence; however she presented subsequent neurological impairment and finally died 14 days after the last urological procedure. CONCLUSIONS: Transurethral packaging of the urinary bladder in a woman with massive hematuria is a hemostatic option that we recommend to be used before other more dramatic or invasive options are chosen.

Amyloidosis↗
PubMed2005

[Secondary bladder amylodosis with severe recurrent hematuria: transurethral Mikuliz procedure as hemostatic option].

OBJECTIVES: Primary localized amyloidosis of the urinary bladder generally has a benign course. On the contrary, secondary amyloidosis, a consequence of systemic amyloidosis, may have massive bleeding and produce complications such as bladder rupture or lifethreatening hemodynamic problems requiring desperate hemostatic procedures such as hypogastric artery embolization or ligature, or cystectomy. We report one case in which hemostasis was achieved by a Mickulicz transurethral bladder tamponage. METHODS: 58 year old female with very aggressive rheumatoid arthritis and secondary renal amyloidosis under chronic hemodialysis presenting with severe hematuria after hip replacement. An inflamed bladder was found, the biopsy of which showed edema in all layers with blood vessel walls enlarged by amiloyd deposits. After several unsuccessful transurethral hemostatic procedures, intravesical formalin irrigation was carried out together with a Mikulicz type gauze packaging after urethral dilation. The gauze was withdrawn three days later without bleeding recurrence; however she presented subsequent neurological impairment and finally died 14 days after the last urological procedure. CONCLUSIONS: Transurethral packaging of the urinary bladder in a woman with massive hematuria is a hemostatic option that we recommend to be used before other more dramatic or invasive options are chosen.

Amyloidosis↗
PubMed2000

Hemostatic defects in massive transfusion: rapid diagnosis and management.

Severe hemostatic defects that occur during massive transfusion are related to the volume of blood transfused, preexisting hemostatic abnormalities, concomitant pathologic changes, and therapeutic maneuvers. The relative role of each factor in the bleeding can be rapidly determined by using routine clinical laboratory tests. This determination requires an understanding of the properties of selected clotting factors, what coagulation screening tests measure, how these tests behave as the levels of factors change, and test profiles characteristic of different defects. Screening tests include platelet count, prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen level. These tests are generally available on an emergent basis and can be completed within 25 minutes. The pattern associated with hemodilution is universal in massive transfusion. Patterns characteristic of the other pathologic processes that may be encountered are simply superimposed on the characteristics of hemodilution. Successful management of the contributing causes of bleeding depends on the administration of the appropriate blood components in the dose necessary to ensure that the levels of platelets and clotting factors are returned to and maintained at hemostatic levels.

Blood Coagulation Disorders↗
PubMed2000

An evaluation of the hemostatic effect of externally applied notoginseng and notoginseng total saponins.

No effective hemostatic agents are available for external use. This project was conducted to evaluate the hemostatic effects of notoginseng using a hemorrhagic rat model. Rats (n = 40) were divided into four groups, and their tails were transected 5 mm from the tip. Group 1 received no treatment (control), while the other groups received external powder applied to the wound. Group 2 received placebo (flour), group 3 received ground notoginseng, and group 4 received a saponin extract of notoginseng. The total bleeding time was determined and compared between groups. The notoginseng group had lower bleeding times (9.60 +/- 1.50 min) than the control group (19.23 +/- 4.09 min, p < 0.001) or the placebo group (15.18 +/- 2.24 min, p < 0.001). Likewise, the saponin extract group had significantly lower bleeding times (11.70 +/- 2.53 min) than the control and placebo groups (p < 0.001 for both comparisons). No differences were found between the notoginseng and the saponin extract groups (p = 0.35). Notoginseng and a saponin extract from notoginseng provide hemostatic effects when applied externally.

Analysis of Variance↗
PubMed2001

Hemostatic risk factors for atherothrombotic disease: an epidemiologic view.

A number of prospective epidemiologic studies have now tested the hypothesis that plasma measures of hemostatic factors measured in initially healthy subjects may predict the future onset of atherothrombotic events. Epidemiologic evidence is very strong that plasma fibrinogen is a risk marker, if not a causal factor, for atherothrombotic events. Evidence is mixed on whether factor VII, factor VIII, von Willebrand factor, or other coagulation markers predict incident atherothrombosis. D-dimer is emerging as a strong risk marker, as are several fibrinolytic markers such as tPA antigen--but not PAI-1. Despite suggestive studies, no genetic polymorphism influencing hemostatic factor levels has emerged as a consistent and strong risk factor for atherothrombosis. Thus, prospective epidemiologic studies have identified several potential hemostatic markers of atherothrombosis risk, but their causal role and clinical utility in risk prediction remain incompletely established.

Arteriosclerosis↗
PubMed2001

[Clinical significance of hemostatic molecular markers in acute leukemia].

OBJECTIVE: To study the changes of hemostatic molecular markers in acute leukemia (AL) for elucidating their clinical significance. METHODS: A series of hemostatic molecular markers, including TF, TFPI, TAT, PAP, u-PA and u-PAR were measured in 82 acute leukemia. RESULTS: The plasma levels of TF, TAT, u-PA and u-PAR were elevated significantly at diagnosis in all AL patients tested, while TFPI, PAP did only in AML. After treatment, TF and TAT remained high in AML, u-PA and u-PAR were still high in un-remission patients. PAP and u-PA remarkably elevated in patients with severe hemorrhage. CONCLUSIONS: There existed hemostatic abnormality as well as hyperfibrinolysis, which varied with leukemia types and was ameliorated with clinical improvement. The measurement of TF, TAT and PAP may provide useful information for the diagnosis of DIC. u-PA and u-PAR may be considered as a useful indicator for prognosis. Patient with severe hemorrhage should be treated with antifibrinolysis drugs. The prevention of hypercoagulability after treatment should be kept in mind.

Acute Disease↗
PubMed2002

A novel hemostatic agent: the potential role of recombinant activated factor VII (rFVIIa) in anesthetic practice.

PURPOSE: To review the role of recombinant factor VIIa in anesthetic practice. SOURCE: A review of the published literature. MAIN FINDINGS: The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. In addition to its indication for use in patients with hemophilia, use of rFVIIa for treatment of uncontrolled massive hemorrhage in various peroperative settings appears to be rational, safe, and effective. Published results suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure in addition to surgical hemostatic techniques There is preliminary evidence that hemorrhagic complications (eg. epistaxis, vaginal bleeding) associated with profound thrombocytopenia can be reversed with rFVIIa even at platelet counts below 10,000 per microL. Various case reports outlining the successful treatment with recombinant factor VIIa of patents experiencing intractable bleeding after valve replacement surgery, and with severe hemorrhage during therapy with left ventricular assist device, indicate the potential therapeutic efficacy of this agent in cardiac surgical procedures. Additionally, rFVIIa has been used successfully for treatment of massive postoperative bleeding following general surgery. CONCLUSIONS: rFVIIa is a novel hemostatic agent that shows promise in non-hemophiliac patents of a significant therapeutic role in variety of coagulopathic and hemorrhagic conditions in clinical situations ranging from thrombocytopenia, disseminated intravascular coagulation and transfusion-related coagulopathy, as well as in patients experiencing massive blood loss undergoing orthotopic liver transplantation, cardiac, orthopedic and genitourinary surgery.

Blood Coagulation Disorders↗
PubMed2003

[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs].

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)

Fibrinolytic Agents↗