NSAIDs and Gastrointestinal Bleeding: Appraisal of a Case Study

Introduction
Peptic ulcer is a clinical condition that is featured by thinning of the mucosal layers in the fundus of the stomach and duodenum. Peptic ulcer results from excess secretion of hydrochloric acid from the parietal cells of the stomach. Zollinger-Ellison syndrome and dietary habits also increases the risk of peptic ulcer. Peptic ulcer is often associated with abdominal pain and gastrointestinal bleeding. Gastrointestinal bleeding is featured by malena and hematemesis. Non steroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed for managing pain and inflammation. Such medications are also used as prophylactic measures for reducing the risk of myocardial infarction (MI). However, NSAIDs increase the risk of peptic ulcer. Aspirin (acetylsalicylic acid) is one such medication that is used to prevent MI. Myocardial infarction results due to inadequate blood supply to the myocardium. Inadequate blood supply occurs due to formation of blood clots within the coronary capillaries (Bibbins-Domingo, 2016). Platelet activation and aggregation increases the risk of thrombus (clot) formation. Aspirin prevents thrombus formation by reducing platelet activation and aggregation. Thromboxane A2 (TXA2) is one of the major activators of platelets. TXA2 is formed from arachidonic acid in platelets (Bibbins-Domingo, 2016). Cyclooxegenase mediates the conversion of arachidonic acid into TXA2. Aspirin inhibits cyclooxygenase and thereby prevents platelet aggregation and activation.

However, aspirin also increases the risk of systemic bleeding (Bibbins-Domingo, 2016). The present article appraised a case study related with prophylactic consumption of aspirin.
Brief Case History
The case study reflected in this present article pertained to Mrs. Miller. She had a history of regular aspirin use. She consumed aspirin for reducing the risk of myocardial infarction. Mrs. Miller presented with tachycardia, fatigue, hematemesis and malena. The clinical symptoms indicated that Mrs. Miller might be suffering from peptic ulcer.
Appraisal of the Case Study
The case study indicated that Mrs. Miller suffered from peptic ulcer. The ulcer developed due to loss of mucosal protective effects of prostaglandins. The mucosal protective effects of prostaglandins were altered due to regular consumption of aspirin. Hence, it was not appropriate for Ms. Miller to take regular dose of aspirin as per the advice of her neighbor. Prostaglandins are formed from arachidonic aid within the parietal cells of the stomach. Cyclooxygenase converts arachidonic acid into prostaglandins. Prostaglandins protect the gastric mucosa by preventing the formation of excess HCl. Prostaglandins inhibit cAMP mediated efflux of chloride ions. Reduced secretion of chloride ions prevents HCl formation within the gastric lumen (Fink, 2011). As a result, the mucosal layers in the fundus of the stomach and duodenum are not eroded (Najm, 2011). However, NSAIDs (like aspirin) inhibit cyclooxygenase and reduces the formation of prostaglandins. As a result, the mucosal layers in the fundus of the stomach and duodenum were eroded. Erosion of mucosal layers within the fundus and duodenum is referred as peptic ulcer (Yeomans, 2011). The sudden bleeding was associated with breakdown of blood capillaries in the mucosal lining. Moreover, aspirin is a blood-thinner and increases the chance of bleeding by preventing platelet aggregation and activation (Najm, 2011).
Although abdominal pain is a classical warning signal of peptic ulcer, Mrs. Miller did not experience such pain. Abdominal pain results from stimulation of nociceptors by different inflammatory mediators and noxious stimuli. Prostaglandins are inflammatory mediators, which causes pain and inflammation. Since aspirin reduces the formation of prostaglandins, Mrs. Miller did not experience abdominal pain. The other risk factors that could increase the risk of peptic ulcer are presence of Helicobacter pylori infection, increased consumption of alcohol, history of smoking, presence of stress and anxiety, and altered dietary habits (Fink, 2011). On the other hand, presence of Zollinger-Ellison syndrome may also increase the risk of peptic ulcer. Zollinger-Ellison (ZE) syndrome refers to a tumor of the G-cells of the stomach. G-cells secrete a gastrointestinal hormone called gastrin. Gastrin acts on parietal cells and stimulates HCl formation. Hence, ZE syndrome leads to excess HCl formation (Najm, 2011).
The presence of peptic ulcer was confirmed from the physical and laboratory findings. These findings are represented in Table 1.
Laboratory Findings Ms. Miller Normal range Possible cause/s
Red Blood Corpuscles 2.53 million per cubic millimeter 4 to 5.5 million per cubic millimeter The RBC count is significantly lower in Mrs. Miller. The reason for low RBC count could be attributed to the gastrointestinal bleeding (manifested as malena and hematemesis). Gastrointestinal bleeding leads to increased blood loss and reduction in RBC count.
Hemoglobin 8.97 gram/dl 14 to 16 gram/dl Reduction in RBC count also accounts for reduced total hemoglobin concentration. The hemoglobin concentration reflects that Mrs. Miller was suffering from anemia. Anemia results from increased blood loss.
Hematocrit 28.5% 38% to 42% Hematocrit value represents the volume of blood that is occupied by RBCs. Since the RBC count was reduced, it accounted for the lower hematocrit. value
Mean Corpuscular Volume (MCV) 65fl 78 to 90fl MCV represents the average volume of a single RBC. RBC volume is strongly correlated with hemoglobin content. Reduction in hemoglobin content accounted for low MCV.
Mean Corpuscular Hemoglobin (MCH) 21 pg/cell 27 to 32 pg/cell MCH represents the concentration of hemoglobin in a single RBC. Since, the hemoglobin content was reduced, it accounted for the low concentration of hemoglobin/RBC. MCH concentration is reduced in conditions like hemolytic anemia.
White Blood Corpuscles 13,000 per cubic millimeter 4,000 to 11,000 per cubic millimeter The WBC count was higher in Mrs. Miller. It indicates that Mrs. Miller might suffer from certain infections. As per the clinical condition of Mrs. Miller, it is likely that there could be a probability of H. pylori infection.
Neutrophils 75% 50% to 70% Neutrophil count was also higher in Mrs. Miller. Increased neutrophil count confirmed the presence of infections.
Basophils 2% 0 to 1% Basophil count was slightly higher, which again confirms presence of infection.
Monocytes 10% 2% to 6% Monocyte count was higher, which again confirms presence of infection.
Platelets 4,50,000 per cubic millimeter 1, 50, 000 to 4,00,000 per cubic millimeter The platelet count was high indicating that Mrs. Miller might be suffering from hemolytic anemia. Moreover, presence of infections may also account for the increase in platelet count.
Blood Urea Nitrogen (BUN) 23mg/dl 23mg/dl Increased BUN signifies presence of renal disease. However, BUN may be also increased in conditions like hypovolemia and gastrointestinal hemorrhage.
Creatinine 1.1 mg/dl 0.5 to 1.5 mg/dl Creatinine count was normal indicating that there was no renal failure.
Total bilirubin 2.3mg/dl 0.3 to 1.9 mg/dl Increased total bilirubin content might have resulted from increased hemolysis.
Table 1: Laboratory findings and possible causes
The laboratory findings indicated that Mrs. Miller suffered from blood loss. Moreover, Mrs. Miller could be also suffering from certain infections. As a result, there was a marked increase in the percentage of phagocytic cells (like neutrophils, basophils and monocytes) (Wang & Peura, 2011). The renal function was preserved in Mrs. Miller, as confirmed by normal serum creatinine level. However, the BUN levels were high due to hypovolemia (reduced blood volume) and gastrointestinal hemorrhage. The reduced blood volume must have stemmed from malena (presence of blood in stool) and hematemesis (vomiting out blood). On the other hand, the total bilirubin content was higher. Increased total bilirubin content might have resulted from hemolytic anemia (which was confirmed by low MCV count). Hemolysis leads to increased catabolism of hemoglobin. Bilirubin is the catabolic end product of hemoglobin metabolism. Hence, the total bilirubin content was high in Mrs. Miller (Milosavljevic et al., 2011).
Discussion and Conclusion
Non steroidal anti-inflammatory drugs (NSAIDs) are used for reducing the risk of myocardial infarction. However, they also increase the risk of peptic ulcer in concerned individuals. The present case study reflected an incidence of peptic ulcer associated with increased consumption of aspirin. The concerned individual consumed aspirin regularly for reducing the risk of myocardial infarction. However, the individual developed peptic ulcer due to reduced prostaglandin synthesis. The individual also presented with malena and hematemesis that indicated episodes of gastrointestinal bleeding. However, the individual did not experience any abdominal pain. Such situation might have stemmed from a reduction in inflammatory mediators. The individual suffered from hemolytic anemia and a marked reduction in the blood indices (MCV and MCH). Hemolytic anemia led to increased hemoglobin metabolism, which was featured by increased bilirubin content. There was a marked increase in the percentage of phagocytic cells (like neutrophils, basophils and monocytes). This suggests that the concerned individual might be suffering from certain infections. An increase in BUN correlated with increased hemolysis and increased gastrointestinal hemorrhage.
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