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sábado, 10 de julio de 2010

75.-TOXICOLOGICAL PATHOLOGY. I.- ACUTE ATHEROSCLEROTIC PLAQUES EMBOLIZATION AS COMPLICATION OF THROMBOLYTIC THERAPY.REPORT OF A FATAL CASE.PROF.GARFIA.A

75.I.-
ACUTE FATAL ATHEROMATOUS  DEBRIS EMBOLIZATION, INCLUDING CHOLESTEROL CHRYSTALS, AFTER THROMBOLYTIC THERAPY. PROF.GARFIA.A

75.I.-
EMBOLIZACIÓN AGUDA FATAL DE FRAGMENTOS DE PLACAS DE ATEROMA -INCLUYENDO CRISTALES DE COLESTEROL- DURANTE TRATAMIENTO TROMBOLÍTICO APLICADO EN INFARTO AGUDO DE MIOCARDIO.  
PROF.GARFIA.A


INTRODUCTION
     Pathology is the science of disease. It is the study of the causes of cell and tissue injury and the ways in which cell and tissues respond to injury. The scope of the Legal Medicine is  the study of the  relationships between the cause and effect of injury. There are many causes of cell and tissue injury, including biological agents such as viruses and bacteria and physical causes such as extreme heat or cold. Toxicology is concerned predominantly with one class of causal agents (chemicals) and their effect on living systems. The reaction to the injury is usually seen as changes in cell or tissue function,   as changes in structure  or as morphofunctional changes. Chemically induced structural changes are the main effect of interest in Toxicological Pathology. 

Thrombolytic therapy

 Thrombolytic agents (alteplase, anistreplase, duteplase, lanoteplase, reteplase, saruplase, staphylokinase,streptokinase, tenecteplase, urokinase), are plasminogen activators which cleave the Arg-Val bond of plasminogen resulting in the formation of plasmin, an enzyme that degrades fibrin clots. Plasmin degrades fibrin clots, plasma proteins, and some coagulation factors. Althoug these agents increase fibrinolysis, they have different sites of actions and duration of effect. These agents are used to lyse obstructive thrombi and restore blood flow in occluded blood vessels. Two of the most  commonly used drugs during the thrombolytic therapy are   Streptokinase and Alteplase.  
   Streptokinase is a protein (co-enzym) isolated from cultures of group C, beta-hemolytic streptococci. Available forms for streptokinase are: 1.5 millon IU lyophilized powder for infusion 1.500.00 IU, 250.000 IU, 600.000 IU, 750.000 IU powder for injection.
  Alteplase is a glycoprotein enzyme obtained by recombinant DNA technology utilizing the complementary DNA for natural human tissue-type plasminogen activator from a human melanoma cell line. Available forms for Alteplase are 50mg and 100 mg powder for injection.
Thrombolytics are used in the treatment of thromboembolic disorders such as myocardial infarction, peripheral arterial thromboembolism, and venous tromboembolism - deep vein thrombosis and pulmonary embolism. Also are used to clear blocked cannulas and shunts.

THROMBOLYTIC THERAPY COMPLICATIONS

     The most common complications observed with thrombolytic therapy are:
1.-Haemorrhages
     Combined exudative retinal and choroidal detachments with suprachoroidal haemorrhage have been described.
Hemoptysis and hemothorax have been described in some patients after the administration of alteplase or streptokinase.
2.-Reperfusion dysrhytmias 
   (Bradycardia, idioventricular rhythm, ventricular tachycardia and ventricular fibrilation) should be anticipated in patients receiving thrombolytic therapy for acute myocardial infarction.
3.-Vascular oclussions (acute or chronic arterial oclussions or cholesterol crystal embolization 
       Ocurred after alteplase thrombolysis procedure or after streptokinase infusions  for chronic arterial occlusive diseases).
4.-Myocardial rupture and Hemopericardium.
    Myocardial  ventricular rupture may ocurred after successful streptokinase recanalization.Streptokinase may cause reperfusion injury and convert a bland infarct to a haemorrhagic infarct. Ischemia may then extend beyond the initial area of necrosis resulting in possible cardiac rupture.
Hemopericardium causing cardiac tamponade has been observed following intravenous streptokinase for the treatment of pulmonary embolism.
5.-Respiratory Distress Syndrome. 
      Elevated levels of fibrinogen degradation product may be responsible for this pulmonary complication.
6.- Pulmonary embolism.
7.- Intracranial Bleeding.
8.- Guillain-Barre Syndrome.
9.- Gastrointestinal bleeding.
10.-Splenic rupture.
11.-Hepatotoxicity and Nefrotoxicity.
  Jaundice and hepatitis-like reaction, and acute tubular necrosis have been described in some patients.
12.-Anaphylactic reactions have been observed rarely. 
  Elevated levels of specific IgE and IgG levels were demonstrated in vivo (cutaneous immediate-hypersensitivity with flare reactions).

DRUG INTERACTIONS
   1.-Contemporay administration of thrombolytic agents with oral anticoagulants is contraindicated.
  2.-Concurrent administration of thrombolytic agents with drugs known to significantly affect platelet integrity, should be avoided:
phenylbutazone.
Indometacin.
Aspirin.





Histopatología Forense Práctica
BLOOG 75.-FOTO 1
PROF.GARFIA.A

Fig.1.-Acute vascular oclussion. 
    Microscopic Panoramic View of atherosclerotic plaques embolization, affecting two  interstitial arterioles supplying skeletal muscle, after intravenous streptokinase infusion given for myocardial infarction. Cholesterol crystal (star). M=skeletal muscle.
Prof. Garfia.A


Histopatología Forense Práctica
BLOOG 75.-FOTO 2
PROF.GARFIA.A

Fig. 2.-Acute cholesterol crystal embolism. 
  Microscopic transversal section of an arteriole showing cholesterol crystal embolization (star), from the same patient, a 69 -year- old man, being treated for acute myocardial infarction with intravenous streptokinase. He developed an abrupt pain in his first left toe, followed immediately by livedo reticularis over his lower extremities and lower abdomen.After five hours the patient died.
Prof. Garfia.A
"From a morphological point of view, the images displayed cholesterol crystals correspond strictly to the graves left by the crystals to be dissolved by the solvents used during the  histological technique."



Histopatología Forense Práctica
BLOOG 75.-FOTO 3
PROF.GARFIA.A


Fig.3.- Acute atherosclerotic plaque embolization -including cholesterol crystal embolization (stars) - occurred as fibrinolysis destroys the adherent platelet-fibrin (F) trombi normally covering ulcerated atherosclerotic plaques. Distal arterial embolization to numerous organs ocurred after intravenous streptokinase administration. Cholesterol embolism is a rare but notable complication of thrombolytic terapy that  is associated with a high mortality rate.
Prof. Garfia.A