Clinical Biochemistry - Case Study Example

 Clinical Biochemistry Case Study Introduction James, aged 56 years, male was found collapsed and incoherent in the street. He was complaining of chest pain. He was brought by the paramedics to the ER who attributed the bruises on the side of the body to trauma sustained by fall. Emergency clinical biochemistry laboratory tests indicated elevated CK, AST, and LDH. The junior doctor concluded a diagnosis of myocardial infarction and without consulting a senior doctor administered streptokinase, and four hours later, the patient sustained a stroke and expired. Case Study The symptoms caused by heart disease result most commonly from myocardial ischemia, from disturbance of the contraction and/or relaxation of the myocardium, or from obstruction to blood flow. Ischemia is manifest most frequently as chest discomfort, which James was having while reduction of the pumping ability of the heart commonly leads to hypotension or syncope, which may be the cause of collapse. Indeed as in the case of James, ischemic heart disease, which is by far the most common form of heart disease in adults, may present with chest discomfort which may be the result of myocardial infarction. Although the clinical history fits with the junior doctor's decision, before taking the decision of administering streptokinase, the doctor would have consulted with the consultant, since the results of biochemical tests in establishing a diagnosis of myocardial infarction may be very misleading in such cases, where even terminal catastrophe may occur. The ECG is the cornerstone in the diagnosis of acute myocardial infarction (MI). The biochemical test results must be interpreted in light of the findings in the ECG, although both the sensitivity and specificity are limited, but a normal ECG is uncommon in a case of established myocardial infarction, and the junior doctor did not do an ECG. Before taking a decision of administering streptokinase, it would have been mandatory to establish the diagnosis of acute MI and to rule any bleeding lesion, and these tests were not done. The CK has been done, which is found to be elevated to 250 U/L against 20-200 U/L but in this case more specific CK-MB and Troponin-I would have been advised. The ideal course would have been admit to patient to the hospital and monitor him for deterioration and ECG. Serial markers would have indicated deterioration. Creatine phosphokinase (CK) rises within 4 to 8 h and generally returns to normal by 48 to 72 h. An important drawback of total CK measurement is its lack of specificity for STEMI, as CK may be elevated with skeletal muscle trauma, which may be the case in this patient who sustained a fall, trauma, and bruises. This may lead to a 2 to 3-fold elevation of CK, which commonly leads to ambiguity and erroneous diagnosis of myocardial infarction. Even initially James could have sustained a stroke which is also a cause of elevated CK. CK-MB is advised in such cases to pinpoint the diagnosis since it is more sensitive and specific for myocardial infarction due to its absence in extracardiac tissues. The differentiation between muscle trauma and myocardial infarction origin of CK-MB can be done through calculation of relative index of CKMB mass: CK activity. If this is 2.5, a diagnosis of MI is favoured. Again in case of a skeletal muscle injury which may be the initial situation at James' presentation, this ratio is less useful due to elevation in level of total CK. The elevated AST and LDH have been obviously wrongly correlated to the myocardial infarction since these values per se are nonspecific for myocardial infarction. This is probably right since the time course of these elevations suggest that these were found to be elevated following 2 hours 35 minutes from the initial incident of fall. The values are directly related to the amount of injury of the cardiac cells and AST takes 12 hours and LDH takes 18 hours to be elevated following MI if they are due exclusively to MI. Thus given these facts, it must be stated that while the patient actually sustained a stroke and fell down and sustained further trauma to the head and body muscle mass, James' case was wrongly diagnosed to be a case of MI. The elevated AST and LDH can be ascribed to some liver disorder given his further tests and liver enlargement and the muscle trauma. AST isoenzymes have no specific value since they exist almost in all cells in the cytosol and mitochondria and they are elevated in muscle trauma, liver disease, and MI. LDH isoenzymes are increased in MI, but again they are nonspecific since they are increased in both muscle trauma and liver disease. Therefore before arriving at the diagnosis of MI and deciding to administer thrombolytic therapy with streptokinase, the tests that would have been done were CK-MB, CK-MB2, Troponin-I, CKMB mass: CK, LDH-1 isoenzyme band or LDH flip, myoglobin, cardiac telemetry or cardiac monitoring, a two-dimensional echocardiography, and a radionuclide cardiac imaging or even after the patient would have stabilized an angiogram were necessary to establish the diagnosis of MI. At least before going ahead with streptokinase, the contraindications of administering this drug were to be assessed as a mandatory step. The doctor, thus was incorrect in the diagnosis of MI. In a case of MI, if no contraindications are present, fibrinolytic therapy should ideally be initiated within 30 min of presentation for prompt restoration of full coronary arterial patency. Streptokinase is an approved drug for that purpose since it acts by promoting the conversion of plasminogen to plasmin, which subsequently lyses fibrin thrombi which would have occluded the culprit lesion in the affected coronary artery. While the rationale of use of streptokinase was right, since the patient was not proved to be having an MI, this was also an error on the part of the junior doctor. If he would have been correct in diagnosis an MI, this therapy would have reduced the relative risk of in-hospital death and would reduce infarct size, limited LV dysfunction, and reduced the incidence of serious complications such as septal rupture, cardiogenic shock, and malignant ventricular arrhythmias. However, the doctor missed a very important step of investigating about stroke which is a contraindication of administration of this drug. Clear contraindications to the use of streptokinase include a history of cerebrovascular hemorrhage at any time, a nonhemorrhagic stroke or other cerebrovascular event within the past year, marked hypertension indicated by systolic arterial pressure > 180 mmHg and/or a diastolic pressure > 110 mmHg at any time during the acute presentation, and active internal bleeding. As will be indicated later, this patient was having a stroke and trauma with possibility of internal bleeding, which was definitely aggravated with this agent worsening James' condition and leading to death. There is quite a possibility that is a coagulopathy due to liver disorder which had further aggravated the internal cerebral bleeding leading to this catastrophic death. Hemorrhage is the most frequent and potentially the most serious complication. Hemorrhagic stroke is the most serious complication and occurs in ~0.5 to 0.9% of patients being treated with these agents. In the second phase of pathologic studies there is evidence of liver disease indicated by borderline high ALT, moderate increase in ALP, and severe increase in GGT accompanied by elevation of bilirubin. The normal level of CK-MB in the sample indicates there was no myocardial infarction. High levels of ALP, GGT, and hyperbilirubinemia indicate blockade of the bile ducts leading to impairment of bile flow and cholestasis. While ALP for this purpose is nonspecific, the GGT is specific with high sensitivity to point to liver disease due to retention of bile. Given his profile, the chances of nonalcoholic fatty liver or alcoholic fatty liver disease is a possibility which would have increased his prothrombin time and affected his normal coagulability, although with the data given other causes such as gall stones, carcinoma liver, sclerosing cholangitis, biliary cirrhosis, or drug induced liver disease cannot be excluded. While this is irrelevant as to what could be the liver pathology, some test was necessary to establish the presterptokinase coagulation profile of James. Given this interpretation, thus it can be stated that James had preexisting liver disease, jaundice and coagulopathy, although tests such as partial thromboplastin time or prothrombin time was not conducted while obstructive jaundice indicated by elevated GGT, bilirubin, and ALP could have warranted these tests and a liver imaging. The initial event as evident by studies later on was a stroke where there was bleeding in the cerebral arterial arcade. This led to collapse and fall and bruise of the muscles. These led to elevation of CK, AST (which could have been contributed to by the associated liver disease), and LDH. Isoenzyme studies were not done despite they are nonspecific and studies which could establish the diagnosis of MI in this confounding picture. Subsequent administration of streptokinase without considering stroke and possible coagulopathy aggravated the bleeding through lysis of the clot that would have been naturally forming leading to bleeding within the substance of the brain from the site of trauma and impact to the side of the head. Read More