Arterial thrombosis, treatment

Junghans U, Seitz RJ, Wittsack HJ, Aulich A, Siebler M. Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein Ilb/HIa inhibitor report of four cases. Radiology 2001 221 795-801. 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting... 

Tissue plasminogen activator has been used successfully to treat acute myocardial infarction, and the benefits of this treatment are well documented.102,116 This drug, however, does not seem to be superior to other thrombolytics when treating coronary artery thrombosis, and streptokinase may be a more cost-effective method of treating myocardial infarction. Alternatively, t-PA may be more effective than other thrombolytics in its ability to initially reopen cerebral vessels this drug is often used preferentially during ischemic stroke.4,44 Hence, the added cost of t-PA may be justified in this situation. 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

Bates SM, Weitz JI. Direct thrombin inhibitors for treatment of arterial thrombosis potential difference between bivalirudin and hirudin. Am J Cardiol 1998 82 PI 2-PI 8. 

Mattsson C, Bjorkman JA, Abrahamsson T et al. Local proCPU (TAFI) activation during thrombolytic treatment in a dog model of coronary artery thrombosis can be inhibited with a direct, small molecule thrombin inhibitor (melagatran). Thromb Haemost 2002 87 557-562. 

In contrast to unfractionated heparin, the factor Xa inhibitor tick anticoagulant peptide (TAP) effectively inhibited coronary arterial thrombosis in a canine electrolytic injury model (57). TAP was also effective in inhibition of the procoagulant properties of whole blood clots in vitro however, it was stated that TAP might be not optimal due to its slow binding kinetics (54). Meanwhile, several low molecular weight direct factor Xa inhibitors are in clinical development (Table I), some of them specifically for the treatment and secondary prevention of ACS. DX-9065a, ZK-807834 and otamixaban have been intensively characterized in vitro and in vivo and are in clinical investigations for the treatment of acute arterial thrombosis. 

In addition to the presently available treatments, a new concept is evolving that targets and inhibits the prothrombi-nase multienzyme complex on the platelet surface thus inhibiting further thrombin generation in arterial thrombosis. 

Urokinase is intended for intravenous use only and indicated for the treatment of pulmonary embolism, coronary artery thrombosis, and intravenous catheter clearance. Typical dosages in peripheral arterial disease consist of an infusion at a rate ranging from 60,000 lU/hr to 240,000 lU/hr infused directly into the thrombus. 

Duda SH, Tepe G, Luz O, et al. Peripheral artery occlusion treatment with abciximab plus urokinase versus with urokinase alone—a randomized pilot trial (the PROMPT Study). Platelet receptor antibodies in order to manage peripheral artery thrombosis, radiology 2001 221 (3) 689—696. 

Therapeutic uses Originally used for the treatment of deep-vein thrombosis and serious pulmonary embolism, thrombolytic drugs are now being used with increasing frequency to treat acute myocardial infarction and peripheral arterial thrombosis and emboli, and for unclotting catheters and shunts. 

Abciximab is used for prevention of cardiac ischemic events in patients undergoing percutaneous coronary intervention and to prevent myocardial infarction in patients with unstable angina who do not respond to conventional treatment. It has also been used for thrombolysis in patients with peripheral arterial occlusive disease and arterial thrombosis (2). 

Inhibition of plasminogen by tranexamic acid and aminocaproic acid conld theoretically facilitate the development of thrombosis, bnt whether it actnally does so has been the snbject of contradictory reports. Episodes of venous and arterial thrombosis have been reported in association with treatment using either tranexamic acid or aminocaproic acid. These include thrombosis at unusual sites such as mesenteric thrombosis (46), aorta (47), retinal artery occlusion (48), and intracranial arterial thrombosis (49-51), as well as deep vein thrombosis in the legs (52). 

There have been isolated reports of arterial thrombosis in patients or donors treated with G-CSF. In one study, there was more frequent and significantly more severe thrombocytopenia in patients who received G-CSF until 2 days before chemotherapy compared with controls, who had post-chemotherapy G-CSF only (41). This suggests that administration of G-CSF before chemotherapy can increase the bone marrow toxicity of the latter, a potentially relevant finding in patients undergoing intensification of chemotherapy with shortening treatment intervals. Isolated cases of thrombocytopenia have been reported in... 

Noel C, Hazzan M, Coppin MC, Pruvot FR, Bridoux F, Lelievre G. Renal transplant artery thrombosis following treatment of allograft rejection with monoclonal anti-CD3 antibodies (OKT3). Transplant Proc 1995 27(4) 2438-2439. 

Anistreplase, a thrombolytic enzyme (30 units by direct IV injection over 2 to 5 minutes), is indicated in the treatment of acnte coronary arterial thrombosis (see Figure 94). 

Streptokinase (1,500,000 lU within 60 minutes by fV infusion) is indicated in lysis of coronary artery thrombosis after acute myocardial infarction streptokinase (250,000 lU by IV infusion pump into each occluded limb of the cannula over 25 to 35 minutes) is indicated in arteriovenous cannula occlusion and streptokinase (250,000 lU IV infusion over 30 minutes) is indicated in the treatment of venous thrombosis, pulmonary embolism, and arterial thrombosis and embolism. 

New hybrids of plasminogen activator have been constructed in attempts to increase the specificity toward fibrin polymers and thereby improve the therapeutic value for treatment of coronary artery thrombosis (143, 144). Plasminogen activators are serine proteases that act on plasminogen to release plasmin, also a... 

The anticlotting drugs are used in the treatment of myocardial infarction and other acute coronary syndromes, atrial fibrillation, ischemic stroke, and deep vein thrombosis (DVT). The anticoagulant and thrombolytic drugs ate effective in treatment of both venous and arterial thrombosis. Antiplatelet dmgs are used primarily for treatment of arterial disease. 

C. Clinical Use The major application of the thrombolytic agents is in the emergency treatment of coronary artery thrombosis. Under ideal conditions (ie, treatment within 1—4 hours), these agents may cause prompt recanalization of the occluded vessel. Very prompt use (ie, within 3 hours of the first symptoms) of t-PA in patients with ischemic stroke appears to result in a significantly better clinical outcome. Cerebral hemorrhage must be positively ruled out before such use. The thrombolytic agents are also used in cases of multiple pulmonary emboli. 

In summary, many of the adverse events associated with bevacizumab treatment appear to be related to its pharmacological action to inhibit VEGF. Some of the adverse events such as inhibition of wound healing were expected pharmacologically mediated toxicides, whereas others (such as arterial thrombosis) were unexpected as both the knowledge of the biology of VEGF and its impact on complex balanced systems developed in parallel with the clinical experience with bevacizumab. 

Garstin IWH, Cooper GG, Hood JM. Arterial thrombosis after treatment with bleomycin and cisplatin. (1990) 300, 1018. 

Levin M-D, Betjes MGH, v d Kwast TH, Wenberg BL, Leebeek FWG Acute renal cortex necrosis caused by arterial thrombosis during treatment fcr acute M omyelocytic leukemia Haematologica (2003) 88, ECR21. 

Type IC leaks occur in cases where an aorto-uni-iliac stentgraft has been deployed, in conjunction with a femoral-femoral bypass graft. An occluder device is then placed in the contra-lateral common iliac artery. Its function is to prevent back filling of the aneurysm from the excluded common iliac artery. The treatment of these leaks requires completion of the intended thrombosis of the common iliac artery. Embolization is the simplest way to complete this, either by passing the occluder and embolizing cranial to it, or, by placing a second occluder device caudal to the original device. 

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