Haemorrhagic infarction

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Both antiplatelet agents (including aspirin) and thrombolytics raise the major problem of haemorrhage with secondary transformation from infarction to cerebral haemorrhage. The clopidrogel study... 

White blood cells readily traverse the blood-brain barrier 12-24 hours after ischaemia and contribute to the excessive production of oxygen free radicals. Eventually the infarcted zone becomes infiltrated with lymphocytes, polymorphs and macrophages. The cytokines released from the macrophages contribute to the injury of the vessel walls and to the consequent oedema, haemorrhage and necrosis. Thus the function of the anti-inflammatory agents is to reduce the initial adhesion of the white blood cells and thereby limit the extent of the inflammatory response. 

Savonitto S, Armstrong PW, Lincoff AM, et al. Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein llb/llla inhibitor therapy in acute myocardial infarction. Dichotomous response as a function of age in the GUSTO V trial. Eur Heart J 2003 24 1807. 

Brandt T, Steinke W, Thie A et al (2000) Posterior cerebral artery territory infarcts clinical features, infarct topography, causes and outcome. Multicenter results and a review of the literature. Cerebrovasc Dis 10 170-182 Cals N, Devuyst G, Afsar N et al (2002) Pure superficial posterior cerebral artery territory infarction in The Lausanne Stroke Registry. J Neurol 249 855-861 De Freitas GR, Carruzzo A, Tsiskaridze A et al (2001) Massive haemorrhagic transformation in cardioembolic stroke the role of arterial wall trauma and dissection. J Neurol Neurosurgery Psychiatry 70 672-674... 

A prospective study of acute cerebrovascular disease in the community the Oxfordshire Community Stroke Project 1981-86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. Journal of Neurology, Neurosurgery and Psychiatry 53 16-22... 

Overdose is common amongst users (up to 22% of heavy users report losing consciousness). The desired euphoria and excitement turns to acute fear, with psychotic symptoms, convulsions, hypertension, haemorrhagic storke, tachycardia, arrhythmias, hyperthermia coronary vasospasm (sufficient to present as the acute coronary syndrome with chest pain and myocardial infarction) may occur, and acute left ventricular dysfunction. Treatment is chosen according to the clinical picture (and the known mode of action), from amongst, e.g. haloperidol (rather than chlorpromazine) for mental disturbance diazepam for convulsions a vasodilator, e.g. a calcium channel blocker, for hypertension glyceryl trinitrate for myocardial ischaemia (but not a p-... 

Adverse effects. Haemorrhage occurs but is less of a problem with low doses of heparin it remains a particular risk in patients treated after failed fibrinol5 c therapy for acute myocardial infarction. Platelet transfusion after cessation of abciximab is necessary for refractory or life threatening bleeding. After transfusion, the antibody redistributes to the transfused platelets, reduces the mean level of receptor blockade and improves platelet function. Thrombocytopenia may occur from 1 hour to days after commencing treatment in up to 1% of patients. This necessitates platelet counts at 2-4 hours and then daily if severe, therapy must be stopped and, if necessary, platelets transfused. EDTA-induced pseudothrombocytopenia has been reported and a low platelet count should prompt examination of a blood film for agglutination before therapy is stopped. 

Pulmonary infarction jaundice following extensive haemorrhagic pulmonary infarction with haemolysis of the erythrocytes which have passed into the alveoli. 

Where coma of cerebrovascular origin is suspected a C.SF examination (Fig. 3) will show the pre.sence of blood and will help to differentiaie a subarachnoid haemorrhage from cerebral infarction. When available, imaging with a CT scan is prefeniblc. 

However, in 1998 the manufacturers of lansoprazole had on record two reports of possible interactions. An elderly patient taking warfarin developed an INR of 7 when lansoprazole was added. Despite a warfarin dosage adjustment he had a gastrointestinal haemorrhage, a myocardial infarction and died after 3 weeks. Another man taking warfarin (as well as amiodarone, furosemide and lisinopril) became confused, had hallucinations and developed an increased INR (value not known) when given lansoprazole. The lansoprazole was stopped after 4 days, and he then recovered. However, it is uncertain whether this was an interaction or whether he had taken an incorrect warfarin dosage because of his confusion. ... 

Acute myocardial infarction results in nearly all cases from thrombotic occlusion of the coronary artery at a point of atherosclerotic narrowing . Histological studies have demonstrated that the thrombus is largely composed of platelets at its point of attachment to the vessel walP°°, suggesting that platelet activation is the initiating event. In addition, the endothelium is frequently disrupted with haemorrhage from the lumen into the atherosclerotic plaque ° Thus, coronary thrombosis may result from platelet activation by exposed subendothelial collagen and subsequent formation of a fibrin clot. 

Suzuki J, Komatsu S, Sato T, Sakurai Y (1980a) Correlation between CT findings and subsequent development of cerebral infarction due to vasospasm in subarachnoid haemorrhage. Acta Neurochir (Wien) 55 63-70 Suzuki J, Kwak R, Katakura R (1980b) Review of incompletely occluded surgically treated cerebral aneurysms. Surg Neurol 13 306-310... 

On NECT, patients with CVT often demonstrate venous infarctions (50%) with cortical/subcortical petechial haemorrhages and oedema. The so-called cord... 

Reversible severe left ventricular systolic dysfunction with apical ballooning has abo been reported during dobutamine stress echocardiography [45, 46, 47, 48, 49, 50, 51, 52, 53, 54 ] and abo in one case after recovery from stress echocardiography [55 ]. In one case it occurred in a patient with previous orthotopic heart transplantation [56 ]. In another case it occurred in a patient who had had a subarachnoid haemorrhage [57 ], in which sympathetic nervous system activity b increased and in which acute myocardial infarction can abo occur. 

Observational studies In a multicenter, observational retrospective review of 127 patients (80 male, mean age 51.7years) who had undergone at least ISmonths of treatment with alpha-l-antitrypsin therapy (Trypsone or Pro-lastin ), there were four serious adverse events that occurred during the treatment period one massive pulmonary thromboembolism, one myeloid leukaemia, one acute myocardial infarction and one haemorrhagic infarcHon but were judged not to be related to treatment. Seven of 11 nonserious adverse events were considered related to treatment including mild to moderate cutaneous symptoms (facial erythema, oedema/pruritus, rash), chills, fever and anxiety [31 ]. 

Observational studies In a multicenter case series, 25 women received recombinant Factor Vila for treatment of severe obstetric haemorrhage [123 ]. A total of 9 patients experienced 11 adverse events within 28days of rFVIIa exanthema (n= 1), fever (n=1), hypopituitarism (n= 1), acute myocardial infarction (n=1), ileus (n = 1), asymptomatic deep vein thrombosis (n=2), asymptomatic PE (n=2) and allergic reaction (n=2). 

Haematologic In a study of rapid warfarin reversal for intracerebral haemorrhage using 3-factor prothrombin complex concentrate (PCC) and recombinant FVIIa, authors report that 2 of the 46 patients experienced thrombotic complications [124 J. Both patients experienced non-ST-elevated myocardial infarction. Notably, one of these occurred with a 2.4-mg dose of recombinant FVIIa and the study protocol was changed to all subsequent patients getting l.Omg of recombinant FVIIa. 

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