Thrombotic events

The proteolytic enzyme thrombin is known to play a ciucial role in the overall thrombotic event leading to... 

Gerh G, VaneUi C, Turn O, Erario M, GardeUini A, Pughano M, Biondi ML (2005) SDEl-3 A gene polymorphism is associated with chronic myeloprohferative disease and thrombotic events. Chn Chem 51 2411-2414... 

Recommendations in this section may change based on the results from the recent EPO-3 trial (epoetin alfa versus placebo). A difference in red blood cell transfusion rates was not observed between groups. Epoetin alpha therapy improved survival in trauma patients. Epoetin alfa did not have a measurable clinical benefit in medical/surgical non-trauma patients. Epoetin alpha therapy was associated with an increased thrombotic event rate, particularly in patients not receiving pharmacological deep vein thrombosis prophylaxis. 

Factor Vila (rFVIIa) is a bypassing agent designed to generate thrombin only at tissue injury sites, where it binds tissue factor and, in this manner, minimizes the risk of systemic thrombotic events. rFVIIa is used effectively in surgeries and spontaneous bleeds.14... 

While bleeding is the most frequently observed symptom of DIC, thrombotic events cause most of the mortality. Heparin is an effective anticoagulant with the potential to inhibit thrombin formation and function however, its use is limited by the potential for bleeding. Clinical trials of heparin in DIC have not shown a consistent benefit. DIC patients most likely to benefit... 

Avasti n ) vascular endothelial growth factor (VEGF) and inhibits angiogenesis. Hypertension, bleeding episodes, thrombotic events Additional toxicities Rare perforation of the bowel, proteinurea... 

Another vasoactive substance produced by the endothelium is thromboxane A2 (TxA2). Normally, small amounts of TxA2 are released continuously however, increased synthesis appears to be associated with some cardiac diseases. Synthesized from arachidonic acid, a plasma membrane phospholipid, TxA2 is a potent vasoconstrictor. Furthermore, this substance stimulates platelet aggregation, suggesting that it plays a role in thrombotic events such as myocardial infarction (heart attack). Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen block formation of TxA2 and reduce formation of blood clots. 

Laboratory tests for hypercoagulable states should be done only when the cause of the stroke cannot be determined based on the presence of well-known risk factors. Protein C, protein S, and antithrombin III are best measured in steady state rather than in the acute stage. Antiphospholipid antibodies are of higher yield but should be reserved for patients aged less than 50 years and those who have had multiple venous or arterial thrombotic events or livedo reticularis. 

The estrogenicity of tamoxifen at several levels brings both advantages and inconveniences. Among the former we have already mentioned bone quality and vaginal proliferation. However, the inconveniences, especially endometrial polyps and cancer and thrombotic events, are important enough to avoid the... 

Celecoxib, a non-steroidal anti-inflammatory drug, is a cyclo-oxygenase-2 selective inhibitor that is as effective as diclofenac and naproxen. It should be used for the shortest period required to control symptoms. Use is associated v/ith an increased risk of thrombotic events and the cyclo-oxygenase-2 selective inhibitors are contraindicated in cerebrovascular disease. Mobic is the proprietary preparation of meloxicam. 

Seizures Seizures have occurred in patients with CRF participating in clinical trials of darbepoetin and epoetin alfa. During the first several months of therapy, closely monitor blood pressure and the presence of premonitory neurologic symptoms. Thrombotic events An increased incidence of thrombotic events has been observed in patients treated with erythropoietic agents. 

The most frequently reported serious adverse events reported with cancer chemotherapy patients included death, fever, pneumonia, dehydration, vomiting, and dyspnea. The most commonly reported adverse events were fatigue, edema, nausea, vomiting, diarrhea, fever, and dyspnea. The most frequently reported reasons for discontinuation of darbepoetin alfa were progressive disease, death, discontinuation of the chemotherapy, asthenia, dyspnea, pneumonia, Gl hemorrhage, thrombotic events, rash, dehydration. 

If thrombotic events occur despite fondaparinux prophylaxis, initiate appropriate therapy. 

Thrombotic events Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported. 

Cardiovascular (CV) risk NSAIDs may cause an increased risk of serious CV thrombotic events, myocardial infarction (Ml), and stroke, which can be fatal. This risk may increase with duration of use. Patients with CV disease or risk factors for CV disease may be at higher risk. 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

Cardiovascular safety. Both drug types promote salt retention, can exacerbate heart failure and tend to raise blood pressure. COX-2 selective drugs also appear to raise the risks of thrombotic events, notably stroke and myocardial infarction, and recent evidence suggests that non-selective NSAIDs also raise these risks, though it is unclear whether to the same degree. For both drug types, dose and duration of treatment appear to affect risk. 

Morbidity and mortality in HIT are related to thrombotic events. Venous thrombosis occurs most commonly, but occlusion of peripheral or central arteries is not infrequent. If an indwelling catheter is present, the risk of thrombosis is increased in that extremity. Skin necrosis has been described, particularly in individuals treated with warfarin in the absence of a direct thrombin inhibitor, presumably due to acute depletion of the vitamin -dependent anticoagulant protein C occurring in the presence of high levels of procoagulant proteins and an active hypercoagulable state. 

Some patients have multiple inherited risk factors or combinations of inherited and acquired risk factors as discussed below. These individuals are at higher risk for recurrent thrombotic events and are often considered candidates for lifelong therapy. 

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

Cyclosporine-A alone and in conjunction with muromonab-CD3 has been associated with seizures, encephalopathy, infection, malignancies, and thrombotic events... 

The use of iloprost has been proposed in patients with systemic sclerosis, a disease that is often characterized by pulmonary hypertension and Raynaud s phenomenon. Three patients with systemic sclerosis who were treated with iloprost developed acute thrombotic events (3). In one case, intestinal infarction occurred 1 day after infusion of iloprost. In another patient the left kidney was not perfused 22 days after the last infusion of iloprost because of thrombosis of the left renal artery. The last patient, 9 months after the start of treatment with iloprost, and 5 days after the last infusion, had an anterolateral myocardial infarction. The authors commented that their observations did not allow them to conclude that there is a direct relation between infusion of iloprost and thrombotic events. However, they said that this possibility should be considered, and they suggested that risk factors for thromboembolism should be carefully evaluated in each patient with systemic sclerosis who is receiving iloprost. 

Tedeschi A, Meroni PL, Del Papa N, Salmaso C, Boschetti C, Miadonna A. Thrombotic events in patients with systemic sclerosis treated with iloprost. Arthritis Rheum 1998 41(3) 559-60. 

Tibolone is an agonist at estrogen and progestogen receptors, with weak androgenic activity. It is given as an alternative to hormone replacement therapy, without added progestogen, and has been in use for some 30 years to treat bone loss in post-menopausal women. Some long-term studies (for example over 10 years) appear to have confirmed its safety and relative freedom from adverse effects (1). In particular there is little or no increase in thrombotic events and the incidence of breast tenderness is low. 

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