Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventeen adult patients who underwent surgery for the thoracic or thoracoabdominal aortic disease by the use of left heart bypass with the Bio-Pump were divided into untreated, low-dose heparin treated and argatroban treated groups so as to evaluate the effects of systemic infusion of a newly synthesized antithrombin agent, argatroban, for the prevention of platelet loss and consumption coagulopathy. ACT reached 150 to 250 seconds at doses 0.5-7.5 micrograms/kg/min of argatroban and maximum ACT prolongation was limited to around 250 seconds. ACT spontaneously recovered below 150 seconds within 60 minutes following the end of bypass during which no excessive blood loss developed. In argartoban group, platelet loss during and immediately after surgery was effectively prevented as compared to other groups with significance. Fibrinogen was also preserved to some extent by argatroban treatment without evidence of systemic embolization. Argatroban, as an antithrombotic agent, is worthy of further trial of clinical use in bypass with a centrifugal pump.
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PMID:[Left heart bypass with the bio-medicus centrifugal pump by the use of an antithrombin agent, argatroban]. 793 35

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.)
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PMID:[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs]. 1457 69

A 75-year-old Japanese woman with polycythemia vera was admitted to our hospital in January 2003 with suspected pulmonary thromboembolism. After administration of heparin, platelet count decreased from 1,694 x 10(9)/l on admission to 60 x 10(9)/l on hospital day 14. The patient developed acute limb embolism and transient cerebral ischemic attack on days 17 and 25, respectively. Signs and symptoms mimicked those of disseminated intravascular coagulation. Antibodies against heparin and platelet factor 4 complexes were detected in serum, and a diagnosis of heparin-induced thrombocytopenia and thrombosis was made. Argatroban treatment improved thrombocytopenia and hypercoagulable state.
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PMID:Heparin-induced thrombocytopenia and thrombosis in a patient with polycythemia vera. 1533 86

We have experienced 2 cases of heparin-induced thrombocytopenia during unfractionated heparin treatment for disseminated intravascular coagulation after surgery for an abdominal aortic aneurysm. In the first case, as a symptom of disseminated intravascular coagulation gradually improved with antithrombin concentrates and heparin treatment, mesenteric artery thrombosis suddenly occurred, associated with a >50% decrease in platelet count on the 11th day. Although the platelet counts were increasing due to heparin cessation, clinical symptom and coagulation abnormalities worsened to multiple organ failure. In the second case, the platelet count decreased to <10 x 10(4)/microL on the 13th day after the start of unfractionated heparin anticoagulation along with continuous hemodiafiltration, which was indicated for postoperative renal failure. The extracorporeal circuit clotted frequently under an adequate dose of unfractionated heparin. Serologically, heparin-platelet factor 4 complex antibodies were repeatedly detected by enzyme-linked immunosorbent assay. Argatroban, a direct thrombin inhibitor, was introduced as an alternative to unfractionated heparin, and the platelet count improved with a decrease in titers of the antibodies. Disseminated intravascular coagulation is a common complication in cases of abdominal aortic aneurysm and is usually treated in association with unfractionated heparin. It is important to recognize the onset of heparin-induced thrombocytopenia that acute declines in the platelet count and appearance of thrombosis with positive for heparin-platelet factor 4 complex antibodies would suddenly occur in clinical course of disseminated intravascular coagulation.
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PMID:Heparin-induced thrombocytopenia in two patients undergoing abdominal aortic aneurysm surgery. 1921 78

Thrombosis due to heparin-induced thrombocytopenia (HIT) is rare but has a severe prognosis. Its management is not always easy, particularly in old patients with renal insufficiency. A 95-year-old woman was hospitalized for dyspnea. Curative treatment with unfractionated heparin was started because pulmonary embolism was suspected. Disseminated intravascular coagulation was then suspected because of thrombocytopenia, hypoprothrombinemia, hypofibrinogenemia, and a positive ethanol gelation test. The first immunoassay for HIT was negative. On the 12th day of hospitalization, bilateral cyanosis of the toes occurred associated with recent deep bilateral venous and arterial thrombosis at duplex ultrasound. New biological tests confirmed HIT and led us to stop heparin and to start argatroban with a positive clinical and biological evolution. Venous and arterial thrombosis associated with thrombocytopenia during heparin treatment must be considered HIT whatever the biological test results are. Argatroban is a good alternative treatment in the elderly.
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PMID:Successful management of heparin-induced thrombocytopenia using argatroban in a very old woman: a case report. 2353 31