Upper Gastrointestinal Bleeding (2024)

by Resshme Kannan Sudha & Thiagarajan Jaiganesh

You have a new patient!

A 55-year-old male with alcoholic liver cirrhosis was brought to the emergency department by his wife, presenting with two episodes of haematemesis (containing fresh blood) and light-headedness. This is the first occurrence of such symptoms. Vital signs: Temperature: 36.8°C, Heart Rate: 115 bpm, SpO₂: 95%, BP: 88/65 mmHg. On examination, the patient appears pale, lethargic, and jaundiced, with abdominal distension noted.

The image was produced by using ideogram 2.0.

What do you need to know?

Upper gastrointestinal (GI) bleeding is defined as bleeding occurring above the level of the ligament of Treitz. It is more common than lower GI bleeding [1]. Upper GI bleeding is a significant clinical condition that can lead to morbidity and mortality if not promptly diagnosed and managed. It encompasses bleeding from the esophagus, stomach, or duodenum, often presenting as hematemesis or melena. The importance of recognizing and treating upper GI bleeding lies in its potential to indicate serious underlying conditions. Early intervention is crucial, as the severity of bleeding can lead to hypovolemic shock, necessitating urgent medical care. Upper GI bleeding is a common emergency, with an estimated incidence of 50 to 150 cases per 100,000 individuals annually [2]. The prevalence varies based on demographic factors such as age, gender, and geographical location. The condition is more prevalent in older adults, particularly those over 60 years.

The most common cause is peptic ulcer disease, with duodenal ulcers being the most frequent. Other causes include varices, erosive esophagitis, duodenitis, Mallory-Weiss tear, gastrointestinal malignancies, and arterial and venous malformations (e.g., aorto-enteric fistula, Dieulafoy lesion) [1,3]. Causes of peptic ulcer disease include NSAID (Non-Steroidal Anti-inflammatory Drug) intake, Helicobacter pylori infection, and stress ulcers. In recent years, the incidence of upper gastrointestinal bleeding admissions due to peptic ulcer disease has decreased in the USA. This trend has been attributed to the use of triple therapy for Helicobacter pylori and the co-administration of proton pump inhibitors with NSAIDs [4].

Clinical manifestations include vomiting coffee ground material or fresh blood, and/or passing fresh blood in the stool or black, tarry stool (melena) [1].

Goals in the management of a patient with upper gastrointestinal bleeding include identifying the site and nature of the bleeding, stabilizing the patient, and controlling the source of the bleed [4].

Medical History

After performing a primary survey and stabilizing the patient, it is important to fine-tune your history, physical examination, and investigations to identify the source of bleeding and guide further management and disposition.

Upper GI bleeding commonly presents with haematemesis (coffee-ground or fresh blood), haematochezia, and/or melena [4]. Certain foods, such as beets, and medications like cefdinir, can cause red-colored stool, while bismuth and iron supplements may cause black-colored stool [4].

Associated Symptoms
  • Peptic ulcer disease may be associated with epigastric pain (gastric ulcer) and dysphagia, gastroesophageal reflux disease (GERD), or odynophagia (esophageal ulcer).
  • Haematemesis associated with retching may indicate a Mallory-Weiss tear.
  • The presence of jaundice and ascites suggests variceal bleeding [4].

A prior history of GI bleeding should be assessed, as patients are more likely to bleed from the same lesion.

Key Past Medical History and Risk Factors

Peptic Ulcer Disease:

  • Ulcers can occur in the esophagus, stomach, or duodenum, with duodenal ulcers being more common.
  • However, gastric ulcers account for a higher incidence of bleeding.
  • Known causes include Helicobacter pylori, NSAIDs, alcohol, and steroid use.
  • Symptoms may include epigastric pain, nausea, vomiting, upper GI bleeding (painless haematemesis and melena), and signs of anaemia.
  • Upper GI bleeding after NSAID use, stress, or a history of dyspepsia may indicate erosive gastritis [5,6].

Esophageal Varices:

  • Caused by portal hypertension secondary to liver diseases such as cirrhosis.
  • Symptoms include jaundice, spider angiomata, palmar erythema, hepatic encephalopathy (confusion), coagulopathy (petechiae/purpura), ascites, and variceal bleeding (painless haematemesis with large amounts of fresh blood) [6].
  • Ask about chronic alcohol use, hepatitis, and hepatocellular carcinoma.
  •  

Mallory-Weiss Syndrome:

  • Caused by forceful retching or vomiting, often after heavy alcohol intake.
  • Leads to a tear in the esophagus or stomach, resulting in haematemesis (large amounts of fresh blood).
  • This condition is usually self-limiting [6].

Malignancy:

  • Gastric cancers may present with haematemesis, anaemia, and dyspepsia [6].
  • Enquire about sudden weight loss, loss of appetite, and risk factors like prior Helicobacter pylori infection.

Angiodysplasia:

  • Dieulafoy’s disease is a rare vascular malformation affecting young individuals.
  • It involves small aneurysms in the stomach that rupture, leading to massive spontaneous haematemesis [6].

Aorto-enteric Fistula:

  • A rare condition, usually occurring post-repair of an abdominal aortic aneurysm.
  • Presents with profuse haematemesis and rectal bleeding [6].

Gastro-enteric Anastomosis:

  • Ulcers may develop at the site of gastro-enteric anastomosis, presenting with upper GI bleeding [7].
Comorbid Illnesses

Enquire about conditions such as:

  • Ischemic heart disease or pulmonary conditions (higher haemoglobin levels required).
  • Coagulopathies (may necessitate additional therapies).
  • Dementia or hepatic encephalopathy (risk of aspiration due to altered mental state).
  • Heart failure or renal failure (risk of fluid overload during blood transfusion).
Medication History

Assess for [8]:

  • NSAIDs (associated with peptic ulcers).
  • Anticoagulants and antiplatelets.
  • Chemotherapeutic agents.
  • Iron supplements (black stool).
Symptoms of Severe Bleeding and Poor Prognosis [1,4,7,9]
  • Light-headedness, confusion, syncope (cerebral hypoperfusion).
  • Chest pain and palpitations (coronary hypoperfusion) .

Physical Examination

The severity of bleeding should be assessed based on clinical signs of shock rather than the color of the blood [4]. Upper GI bleeding typically presents with haematemesis (frank blood or coffee-ground emesis) and/or melena [4]. In cases of brisk upper GI bleeding, the patient may present as vitally unstable with haematochezia [4].

Vital Signs

Monitor for signs of hemodynamic instability, including:

  • Tachycardia, tachypnea, and hypotension [1,7].
  • Supine hypotension is associated with greater blood loss than orthostatic hypotension [1].

General Examination

  • Confusion may indicate hemodynamic instability.
  • Gynecomastia may be seen in patients with liver disease [10].
  • Haematemesis strongly suggests an upper GI bleed [4].

ENT Examination

  • Inspect the nose for epistaxis, which can present as haematemesis if the blood is swallowed [11].

Skin Examination

  • Palmar erythema, spider angiomata, caput medusae, and jaundice are suggestive of liver disease [11].

Abdominal Examination

  • Abdominal tenderness, guarding, rigidity, and rebound tenderness may indicate perforation.
  • The presence of ascites suggests liver disease [4,7].

Rectal and Stool Examination

  • A digital rectal examination and stool analysis can help identify the location of the bleed:
    • Melena typically indicates an upper GI bleed.
    • Haematochezia may suggest a lower GI bleed or a massive upper GI bleed [4].

Alternative Diagnoses

The differential diagnosis for gastrointestinal bleeding includes several conditions that may mimic an upper or lower GI bleed:

  1. Epistaxis: Bleeding from the nose can present as haematemesis if the blood is swallowed. Careful examination of the nasal cavity is essential to rule this out.

  2. Vaginal Bleeding: In some cases, vaginal bleeding can be mistaken for haematochezia. A thorough history and physical examination can help differentiate these sources.

  3. Food-Induced Discoloration: Certain foods may alter the color of stool, leading to a false suspicion of GI bleeding. For example, beets can cause red-colored stools, which may mimic haematochezia.

  4. Medication-Induced Changes: Some medications can also discolor stool:

    • Cefdinir may produce red-colored stool.
    • Iron supplements and bismuth-containing products can result in black stool, resembling melena [4].
  5. Neonatal Swallowed Blood: In neonates, vomiting swallowed maternal blood during delivery or breastfeeding may be mistaken for upper GI bleeding [12].

Acing Diagnostic Testing

Bedside Tests

Several bedside tests can aid in the initial evaluation of upper GI bleeding:

  • Point-of-care venous blood gas: Useful for detecting acidosis, electrolyte disturbances, and haemoglobin levels. Haemoglobin levels < 8 g/dL in previously healthy patients, or < 9 g/dL in patients with known coronary artery disease or anaemia-related complications, suggest the need for blood transfusion [4].
  • Point-of-care PT (Prothrombin Time) and INR (International Normalized Ratio): Essential for patients taking medications like warfarin to determine the need for reversal agents.
  • Bedside ultrasound: Helpful in identifying ascites, which may aid in diagnosing variceal bleeding.
Ascites in Cirrhotic Patient

Laboratory Tests

The following blood tests are useful when there is a clinical suspicion of upper GI bleeding [4,6,11,13]:

  • Complete Blood Count (CBC): To assess haemoglobin and haematocrit levels.
  • Blood Urea Nitrogen (BUN), Creatinine, and electrolytes: A BUN:Creatinine ratio > 35 is highly suggestive of upper GI bleeding (90%).
  • Coagulation Screen: INR levels are important in patients on anticoagulant therapy (e.g., warfarin) to guide reversal strategies.
  • Liver Function Tests: Elevated parameters are suggestive of liver disease and potential variceal bleeding.
  • Type and Crossmatch: Crucial for patients who may require blood transfusion.

Imaging

Radiological imaging is rarely needed in hemodynamically unstable patients as it may delay resuscitation. In such cases, endoscopy should take precedence [4].

  • Upright chest X-ray: Helpful in detecting free air under the diaphragm, which is suggestive of perforation.
  • CT Angiography: Recommended for hemodynamically stable patients when identifying the bleeding etiology before endoscopy is crucial. It can detect slow bleeding (approximately 0.3 mL/min) and guide management decisions (endoscopy, surgery, or angiography). However, it is not suitable for unstable patients due to delays in management. In such cases, conventional angiography with embolization is preferred [4].

Endoscopy

Endoscopy is both diagnostic and therapeutic [14,15]:

  • There is no evidence to support that emergent endoscopy is superior to routine endoscopy.
  • Immediate gastroenterology consultation for emergent endoscopy is advised in patients with ongoing severe upper GI bleeding.
  • Endoscopy is recommended within 24 hours for all admitted patients with UGIB after stabilizing hemodynamic parameters and addressing other medical issues.
  • Patients with high-risk clinical features such as tachycardia, hypotension, haematemesis, or blood in nasogastric aspirate should undergo endoscopy within 12 hours, as this may improve clinical outcomes.

Additional Considerations

  • A screening ECG is recommended in patients > 35 years of age with cardiac risk factors, as co-existing acute coronary syndrome may complicate GI bleeding [4].
  • Nasogastric lavage is generally not recommended due to risks of perforation, pneumothorax, and aspiration [4].
  • Erythromycin can be used as an alternative prokinetic to clear gastric contents before endoscopy [4,8].

Risk Stratification

To effectively manage gastrointestinal (GI) bleeding, patients must be categorized into high-risk and low-risk groups. High-risk patients require prompt intervention, whereas low-risk patients can be managed through outpatient treatment [4]. A combination of clinical, endoscopic, and laboratory features, along with risk scores, can aid in risk stratification. While risk scores may not always predict high-risk patients accurately, they are effective in identifying patients at very low risk of harm. When selecting patients for outpatient management, ensuring high sensitivity is essential to prevent the inadvertent discharge of high-risk individuals [16].

Risk Assessment Tools

Commonly used scoring systems for GI bleeding include:

  1. Glasgow-Blatchford Score (GBS)
  2. Rockall Score
  3. AIMS65 Score

The AIMS65 score assesses parameters such as:

  • Albumin < 3 mg/dL
  • International Normalized Ratio (INR) > 1.5
  • Altered mental status
  • Systolic blood pressure < 90 mmHg
  • Age > 65 years

Studies show that the GBS is more effective at predicting a combined outcome of intervention or death [16].

Glasgow-Blatchford Score (GBS)

The Glasgow-Blatchford Score is particularly useful for predicting the need for intervention, hospital admission, blood transfusion, surgery, and mortality. A significant advantage of the GBS is that it can be calculated at the time of patient presentation, as it does not require endoscopic data (unlike the Rockall score).

The GBS includes the following parameters:

  • Blood urea nitrogen (BUN)
  • Haemoglobin levels
  • Systolic blood pressure
  • Pulse rate
  • Symptoms such as melena, syncope, and a history of hepatic disease or cardiac failure.

The score ranges from 0 to 23, with a higher score indicating a greater risk of requiring endoscopic intervention [4].

Glasgow-Blatchford Risk Score

CategoryScore
BUN in mg/dL
18.2 to 22.42
22.5 to 283
28.1 to 704
70.1 or greater6
Hemoglobin, men g/dL
12 to 131
10 to 11.93
9.9 or less6
Hemoglobin, women g/dL
10 to 121
9.9 or less6
Systolic Blood Pressure, mmHg
100-1091
90-992
<903
Heartrate >100 peats per minute1
Melena1
Syncope2
Hepatic Diseases2
Heart failure2
Glasgow-Blatchford Risk Score is useful for predictive of inpatient mortality, blood transfusions, re-bleeding, ICU monitoring, and hospital length of stay. Patients with a score of zero may be discharged home, those with score 2 or higher are usually admitted, and those with score of 10 or more are at highest risk for morbidity and resource utilization. Maximum score is 23.
Outpatient Management

Patients with a Glasgow-Blatchford Score of 0 are considered at low risk for rebleeding. According to international consensus guidelines, these patients may be safely discharged with early outpatient follow-up [8,17].

Management

Initial Stabilization

Airway and Breathing:
Patients with massive upper GI bleeding presenting with uncontrollable haematemesis, respiratory distress, or severe shock require immediate airway protection and intubation. It is essential to improve hemodynamic status before administering induction and paralytic drugs for intubation and initiating positive pressure ventilation, as this can mitigate a sharp decrease in cardiac output. However, intubation is associated with poor outcomes and should only be performed when absolutely necessary [4].

Circulation:
Massive GI haemorrhage is characterized by ongoing active bleeding (haematemesis or haematochezia), signs of hemodynamic compromise (e.g., tachycardia, hypotension, altered mental status), or a shock index ≥ 0.9 [4].

Immediate volume resuscitation is critical and includes:

  • Placement of two large-bore IV catheters.
  • Infusion of balanced isotonic crystalloids (e.g., 2 liters of normal saline or Plasmalyte over 30 minutes).
  • Transfusion of uncrossmatched blood, if required [4].
Transfusion Strategies

For stable patients, a restrictive transfusion strategy is recommended. While the ideal haemoglobin target is not universally defined:

  • In stable patients without known coronary artery disease (CAD), maintain haemoglobin ≥ 8 g/dL.
  • For patients with known CAD, a higher target of ~9 g/dL is appropriate to reduce the risk of anaemia-related complications [4].

In patients requiring massive transfusion (more than 4 units of PRBCs), a balanced transfusion ratio of 1:1:1 (PRBC:Platelets:Fresh Frozen Plasma) is advised. Cryoprecipitate should be administered if fibrinogen levels remain < 1.5 g/L [18]. A platelet count > 50,000 platelets/μL should be maintained [4].

Coagulation Management
  • Vitamin K antagonists (e.g., warfarin) should be stopped and reversed to achieve a target INR of 1.5–2.5. Treatment options include Fresh Frozen Plasma (FFP) and Prothrombin Complex Concentrate (PCC). Vitamin K is an appropriate choice for hemodynamically stable GI bleeding.
  • Direct oral anticoagulant reversal:
    • Idarucizumab for dabigatran reversal.
    • PCC or coagulation factor Xa (recombinant/inactivated-zhzo) for factor Xa inhibitors.
  • For heparin reversal, protamine sulfate may be used.

Before administering reversal agents, the risks of reversing anticoagulant therapy must be carefully weighed against the risk of thromboembolism [19].

PCC is preferred over FFP for rapid coagulopathy correction, especially in patients at risk of fluid overload, as it requires lower volume administration [4]. Over-transfusion or empiric correction of PT/INR with FFP or PCC in portal hypertension may worsen portal hypertension and exacerbate bleeding [4].

Medications

Proton Pump Inhibitors (PPIs)

PPIs are the mainstay in the management of acute GI bleeding. They work by inhibiting the hydrogen potassium ATPase pump, thereby reducing gastric acid secretion [20]. Studies have shown that PPIs reduce the risk of re-bleeding, the need for surgery, and mortality in patients with bleeding ulcers [4].

Both intermittent PPI therapy and continuous infusion are equally effective in reducing bleeding [8]. Available IV formulations include esomeprazole and pantoprazole. The recommended dose is:

  • Pantoprazole or esomeprazole: 80 mg IV as a single initial dose, followed by either:
    • Continuous infusion at 8 mg/hr, or
    • 40 mg IV BID [8].

If IV formulations are unavailable, oral alternatives such as 40 mg of esomeprazole twice daily may be used [8].

PPIs are classified as Category B in pregnancy, except for omeprazole, which is Category C [21]. Caution should be exercised due to the risk of Clostridium difficile infection, Steven Johnson syndrome, kidney and liver impairment, and pancreatitis [20]. Omeprazole is particularly associated with the risk of acute interstitial nephritis [22].

Somatostatin Analogues

Somatostatin and its synthetic analogue, octreotide, are predominantly used in variceal bleeding. These agents reduce the risk of bleeding, need for transfusion, and portal hypertension. Indications include acute GI bleeding in patients with variceal bleeding, abnormal liver function tests, liver disease, or alcoholism [4].

The dosing regimen for octreotide is:

  • Adults: 50 mcg IV bolus, followed by 25–50 mcg/hr continuous infusion [23,24].
  • Paediatrics: 1 mcg/kg IV bolus (maximum: 100 mcg), followed by 1 mcg/kg/hr infusion [23,24].

Octreotide crosses the placenta and is expressed in breast milk. Common adverse effects include arrhythmias, pancreatitis, abnormal glucose regulation, and low platelet count [23]. It also crosses the blood-brain barrier [23].

Terlipressin

Terlipressin is a synthetic vasopressin receptor agonist that causes splanchnic vasoconstriction, thereby reducing portal hypertension. It is primarily indicated for variceal bleeding [25].

The recommended dose is 2 mg IV every 6 hours [26]. Terlipressin may cause teratogenic effects (limited data available) [27] and can result in painful hands and feet due to peripheral vasoconstriction [26]. While studies suggest that terlipressin, somatostatin, and octreotide have similar efficacy, data regarding their use in paediatric patients remains limited [24,28].

Prokinetic Agents (Erythromycin and Metoclopramide)

Prokinetic agents are used to improve visualization during endoscopy by clearing gastric contents.

  • Erythromycin:

    • Adult dose: 3 mg/kg IV, administered over 20–30 minutes, 20–90 minutes before endoscopy [29].
    • Classified as Category B in pregnancy and is safe for breastfeeding mothers [29].
    • Adverse effects include QT prolongation, pseudomembranous colitis, seizures, and hypertrophic pyloric stenosis [4,29].
  • Metoclopramide:

    • Adult dose: 10 mg IV.
    • Paediatric dose: 0.1–0.2 mg/kg IV [30].
    • Classified as Category B in pregnancy [30].
    • Caution is advised in patients with a history of extrapyramidal symptoms due to its association with extrapyramidal side effects [30].

Tranexamic Acid

Tranexamic acid is an antifibrinolytic agent. However, according to the HALT-IT Trial, it has not been shown to reduce mortality associated with gastrointestinal bleeding. As a result, its routine use in GI bleeding is not recommended [31].

Antibiotic Prophylaxis

Antibiotic prophylaxis is recommended for patients with cirrhosis or suspected cirrhotic liver disease to reduce the risk of infection and mortality [4].

The recommended antibiotics include:

  • Fluoroquinolones (e.g., ciprofloxacin 400 mg IV)

  • Third-generation cephalosporins (e.g., ceftriaxone 1–2 g IV) [4].

  • Ceftriaxone: Classified as Category B in pregnancy but contraindicated in hyperbilirubinemic neonates due to the risk of kernicterus and those receiving IV calcium-containing solutions due to ceftriaxone–calcium precipitation [32].

  • Ciprofloxacin: Classified as Category C in pregnancy. Adverse effects include Clostridium difficile infection, dysglycemia, tendon rupture, neurotoxicity, QT prolongation, hepatotoxicity, and Stevens-Johnson syndrome/toxic epidermal necrolysis [33].

Procedures

Balloon tamponade [4,6,34], using devices such as the Sengstaken-Blakemore tube, Minnesota tube, or Linton-Nachlas tube, can serve as a temporizing measure for suspected life-threatening variceal bleeding when endoscopy is not immediately available. These devices must be stored in refrigerators to maintain readiness.

Before the procedure, patients must be intubated to reduce the risk of aspiration. The device is inserted through the mouth, passed via the esophagus into the stomach. The tube consists of two balloons—a gastric balloon and an esophageal balloon:

  • The gastric balloon of the Sengstaken-Blakemore tube can be inflated with 250–300 cc of air, while the Minnesota tube can accommodate up to 450–500 cc to secure the tube in place.
  • The esophageal balloon can be inflated to a pressure of 20–40 mmHg, with a strict upper limit of 45 mmHg to avoid injury. Pressure should be carefully monitored using a manometer.

Balloon tamponade is a temporary measure, and definitive management, such as endoscopic therapy, should be arranged as soon as possible. The procedure is associated with significant risks, including ulceration, esophageal rupture, and aspiration [4].

Special Patient Groups

Paediatrics

The causes of upper GI bleeding in the pediatric population are generally similar to those seen in adults [12,15,35]. However, there are additional causes specific to neonates and infants that require consideration. In neonates, vitamin K deficiency, also referred to as the haemorrhagic disease of the newborn, is an important cause. Other causes include congenital vascular anomalies, such as telangiectasia, and coagulopathy, which may result from infections, liver disease, or coagulation factor deficiencies. Milk protein intolerance is also a recognized cause of upper GI bleeding in this age group. During the neonatal period and the first few months of life, it is crucial to differentiate swallowed maternal blood from true upper GI bleeding. The Apt-Downey test is a reliable diagnostic tool used to confirm the presence of fetal blood and rule out swallowed maternal blood as the source.

The management of upper GI bleeding in children largely follows the same principles as in adults, with necessary adaptations for the pediatric population. Intravenous proton pump inhibitors (IV PPIs) are effective and can be administered to reduce gastric acid secretion, thereby promoting hemostasis. In cases of suspected variceal bleeding, somatostatin analogues can be given to reduce portal hypertension and minimize bleeding risk. When severe acute bleeding is ongoing, endoscopy plays a key role in diagnosis and intervention. It is recommended that endoscopy be performed within 24 to 48 hours of presentation. However, it is critical to ensure that the patient is as hemodynamically stable as possible before proceeding with the procedure to minimize complications.

In cases where endoscopy cannot control the bleeding or fails to identify the source, further interventions may be necessary. Angiography with embolization is a useful modality in such instances, as it can help detect and address underlying vascular abnormalities contributing to the bleeding. This approach is particularly helpful when other methods have proven unsuccessful.

Overall, a multidisciplinary approach that includes appropriate stabilization, pharmacologic therapy, and procedural intervention is essential to effectively manage upper GI bleeding in the pediatric population [12,15,35].

Geriatrics

Upper GI bleeding in elderly patients presents unique challenges due to the high-risk nature of this population and the limitations of existing risk assessment tools. Studies indicate that traditional pre-endoscopic risk scores, such as the Glasgow-Blatchford and AIMS65, often fail to accurately predict outcomes like mortality and hospital stay length in geriatric patients, particularly those aged 82 and older, suggesting a need for age-adjusted scoring systems [36]. Despite these challenges, emergency oesophagogastroduodenoscopy is generally safe for elderly patients, with a high survival rate at 90 days post-procedure, although a significant proportion of OGDs yield normal findings, highlighting the importance of careful patient selection [37]. The management of Upper GI bleeding in the elderly is further complicated by recurrent bleeding, as seen in cases involving peptic ulcer disease, which necessitate a multidisciplinary approach and close monitoring to improve outcomes [38]. Recent efforts to develop novel risk scores tailored for the elderly have shown promise, with a new score incorporating factors like comorbidity index and blood pressure demonstrating good discriminative performance for identifying patients suitable for outpatient management [39].

Pregnant Patients

The causes of upper GI bleeding in pregnant women are similar to those in the general population, including conditions such as esophageal ulcers, gastroesophageal reflux disease, and portal vein thrombosis leading to esophageal varices [40]. Haematemesis, or the vomiting of blood, is a common manifestation of upper GI bleeding and can present as bright red or coffee-ground emesis, indicating bleeding from the upper gastrointestinal tract [1, 40]. In rare cases, UGIB in pregnancy can be caused by gastrointestinal stromal tumors (GISTs), as illustrated by a case where a pregnant woman presented with coffee-ground vomiting and was diagnosed with a bleeding GIST at the stomach cardia [41]. Endoscopy is a critical diagnostic and therapeutic tool for upper GI bleeding, but its use in pregnant women is generally reserved for severe or persistent cases due to potential risks to the mother and fetus [42]. Despite the need for endoscopic evaluation in over 12,000 pregnant women annually in the U.S., research on the safety and outcomes of such procedures remains limited [43]. Therefore, careful consideration of the risks and benefits is essential when managing upper GI bleeding in pregnant patients.

When To Admit This Patient

Admission is required for elderly patients over the age of 60 years, those who require blood transfusions, and patients with a Glasgow-Blatchford Score (GBS) greater than 0 [4,8]. Patients with high-risk bleeding sources should be admitted to a monitored setting or an intensive care unit (ICU) to allow close monitoring for signs of rebleeding and other potential complications.

The decision to discharge a patient following endoscopy depends on the identification of the bleeding source and the associated risk of rebleeding. Patients can be considered for discharge if they meet all of the following criteria: a GBS of 0, blood urea nitrogen (BUN) less than 18 mg/dL, haemoglobin >13 g/dL in men and >12 g/dL in women, heart rate less than 100 beats per minute, systolic blood pressure greater than 110 mmHg, no evidence of melena or syncope since the initial presentation, absence of heart failure or liver failure, and prompt access to outpatient follow-up care.

However, it is important to note that this recommendation is based on low-quality evidence, and clinical judgment should play a significant role in the final decision to discharge a patient. Clinicians should carefully assess each patient’s overall condition, risk of rebleeding, and ability to follow up in an outpatient setting to ensure safe discharge planning [15].

Revisiting Your Patient

In managing this patient, the immediate priority is to assess airway, breathing, and circulation and provide stabilization. Given the patient’s vital instability, they should be promptly transferred to the resuscitation bay for further management.

The image was produced by using ideogram 2.0.

Airway and Breathing: The patient’s airway is currently patent, and they are communicating comfortably, with no signs of obstruction such as pooling of blood or secretions. There have been no further episodes of haematemesis, and the patient is maintaining adequate oxygen saturation on room air. Chest auscultation is clear. At this time, the patient does not require airway adjuncts or intubation, but close observation is essential to detect any deterioration.

Circulation: The patient is hypotensive, indicating the need for immediate intervention. Two large-bore IV cannulas should be inserted to initiate intravenous fluid resuscitation. Crossmatched and uncrossmatched blood should be arranged as a precaution. A point-of-care venous blood gas test must be performed to quickly evaluate acidosis, haemoglobin levels, and other critical parameters. Care should be taken to avoid fluid overload, especially in patients with underlying liver disease.

Further History and Review of Systems: On further evaluation, the patient denies haematochezia, haemoptysis, epistaxis, melena, chest pain, palpitations, syncope, loss of consciousness, or confusion.

Past Medical and Surgical History and Risk Factors: The patient has a history of alcoholic liver disease and is a smoker. There is no history of chronic NSAID use, Helicobacter pylori infection, recent forceful retching, or ingestion of foods or medications that might cause red-colored secretions. There are no known coagulopathies, recent anticoagulant use, vascular abnormalities, weight loss, or loss of appetite. Additionally, the patient has no history of prior surgery.

Examination: Clinical signs of hemodynamic instability, such as hypotension, suggest hypovolemic shock, requiring prompt management with IV fluids and blood transfusion. Examination findings of jaundice, abdominal distension with shifting dullness, and caput medusae are consistent with alcoholic liver disease and indicate probable variceal bleeding. There is no abdominal tenderness, guarding, rigidity, or rebound tenderness to suggest another abdominal pathology.

Laboratory Investigations: Laboratory tests sent include a complete blood count, urea, electrolytes, creatinine, coagulation screen, liver function tests, and type and crossmatch for transfusion. The point-of-care venous blood gas reveals acidosis, haemoglobin <8 g/dL, negative base excess, and elevated lactate, indicating ongoing active bleeding. These findings necessitate urgent gastroenterology consultation for endoscopic intervention and the arrangement of blood transfusion. In addition, the patient must be monitored for liver disease-induced coagulopathy, and a haematology consultation is warranted.

Diagnostic Test: The patient’s Glasgow-Blatchford Score is greater than 0, further confirming the need for urgent endoscopy to identify and control the source of bleeding, which is most likely esophageal varices. Simultaneously, resuscitation measures must continue.

Medications: Given the patient’s history of alcoholic liver disease and suspected variceal bleeding, appropriate pharmacological management should include vasoactive agents such as somatostatin, octreotide, or terlipressin to reduce portal pressure. Empirical antibiotics (fluoroquinolones or third-generation cephalosporins) should be administered to reduce the risk of infection. Additionally, proton pump inhibitors (PPIs) should be started as part of the management protocol.

Disposition: This patient requires urgent gastrointestinal consultation for endoscopy to achieve source control of the bleeding. Admission is necessary to allow for close monitoring of potential complications, including rebleeding and complications of alcoholic liver cirrhosis, such as hepatic encephalopathy and renal failure.

Authors

Picture of Resshme Kannan Sudha

Resshme Kannan Sudha

Resshme Kannan Sudha graduated from RAK Medical and Health Sciences University and is currently an Emergency Medicine Graduate Resident at STMC Hospital, Al Ain. She is a keen follower of FOAMed projects and an enthusiastic educator. Her special interests include critical care, POCUS, global health, toxicology and wilderness medicine.

Picture of Thiagarajan Jaiganesh

Thiagarajan Jaiganesh

STMC Hospital, Al Ain

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References

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Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Blood Transfusion And Its Complications (2024)

by Yaman Hukan, Thiagarajan Jaiganesh

You have a new patient!

A 68-year-old male with a history of controlled HTN, DM, and Ischemic heart disease presents to the Emergency Department with complaints of easy fatiguability that started 2 months ago. He reports a gradual onset of symptoms and inability to tolerate his usual morning walk. He denies chest pain or palpitations. Upon further questioning, he mentioned that he noticed his clothes getting loose, and his family noticed he had lost weight. On review of systems, he states he has bouts of diarrhea with dark stools. Upon arrival, his vitals are Temp 36.9 C, HR 105 BPM, BP 122/68 mmHg, RR 17 BPM, and SpO2 of 98% on RA.  Blood investigations reveal an Hgb level of 5.0 g/dL. Therefore, you decide to initiate a Packed RBC transfusion in the ER. One hour after starting the transfusion, you are called by the nurse as the patient is becoming distressed. You attend to the patient and notice him to be in severe respiratory distress.

What do you need to know?

Often, patients presenting to Emergency Departments require a blood transfusion. According to the National Blood Collection and Utilization survey administered by the US Department of Health and Human Services, 2019 around 1 million RBC transfusions took place in EDs across the United States [1]. The clinical conditions necessitating a blood transfusion include upper and lower gastrointestinal bleeding, traumatic shock, symptomatic anemia, etc., to name a few. Therefore, medical trainees and emergency physicians must be aware of complications that may arise from blood transfusions and manage them appropriately.

Commonly administered blood products in the emergency department (ED) include packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelet concentrates, and cryoprecipitate. PRBCs are frequently used to increase oxygen-carrying capacity in patients with significant anemia or hemorrhage. FFP provides essential clotting factors, making it valuable in cases of coagulopathy or massive transfusion protocols. Platelet concentrates are utilized to manage thrombocytopenia or platelet dysfunction, while cryoprecipitate supplies fibrinogen, von Willebrand factor, and other clotting factors, supporting hemostasis in patients with severe bleeding or fibrinogen deficiency.

The choice of components should be directed by the patient’s clinical condition, rate of bleeding, cardiopulmonary status, and operative intervention, with the goal of restoring volume and oxygen-carrying capacity [2].

Administering blood and blood products to patients has resulted in numerous adverse reactions. These reactions are broadly classified as either Acute (onset within 24 hrs), such as febrile nonhemolytic reactions, or Delayed (onset beyond 24 hrs), such as delayed hemolytic reactions [3].

Data from the National Healthcare Safety Network Hemovigilance Module in the United States demonstrate that 1 in 455 blood components transfused was associated with an adverse reaction. However, the incidence of serious reactions was much lower, at 1 in 6224. Despite the relatively lower rates of serious reactions, 23 fatalities were recorded between 2013 and 2018 [4].

Severe adverse reactions result from transfusing incompatible (ABO or Rh) blood. The ABO blood group system remains of extreme importance in blood transfusions, as it is the most immunogenic of all blood group antigens [5]. The four blood groups are A, B, O, and AB.

The table shows the summary of ABO Antigens and Antibodies contained within each blood type.

 

A

B

O

AB

Antigens

A

B

None

A and B

Antibodies

Anti-B

Anti-A

Anti-A & Anti-B

None

There are several ABO blood group antigens expressed on every RBC cell. Each blood group early on during life forms antibodies against ABO antigens not found on the surface of RBCs. When an individual is transfused ABO-incompatible blood, preformed antibodies in its own serum react against the donor’s red blood cells, causing rapid acute intravascular hemolysis, a life-threatening transfusion reaction.

The second significant blood grouping system is the Rh system. The presence of Rh Antigen implies that the patient is Rh(+) (e.g., Blood group O+). Patients who are Rh(-) lack the RhD antigen. Therefore, their blood develops antibodies against Rh(+) blood groups if they are ever exposed to it. This incompatibility can lead to a hemolytic reaction, but it is much less likely than a hemolytic reaction due to ABO incompatibility. The clinical significance of the Rh system lies in the pregnancy setting when a Rh(-) mother is pregnant with an Rh(+) fetus. Upon first exposure to the positive blood from the fetus, the mother’s blood would form antibodies against Rh-blood. In case of a repeated pregnancy with Rh+ fetus, the mother’s antibodies cross the placenta and attack the RBCs of the fetus, which can lead to a condition called hemolytic disease of the newborn [6]. This is the reason why women of childbearing age should always receive O(-) blood in the setting of acute hemorrhage needing a blood transfusion, as opposed to men who may receive O(+) blood safely.

Medical History

Should a patient receiving or recently received a blood or a blood product transfusion develop new signs and symptoms, consider a transfusion reaction. Commonly encountered signs and symptoms of mild transfusion reactions include:

  • Increase in body temperature/fever,
  • Chills/Rigors,
  • Pruritis, New rash, or swelling of the mucous membranes.

Severe reactions include:

  • Difficulty in breathing,
  • Respiratory distress,
  • Altered level of consciousness,
  • Decreased urinary output.

Reaction Types

Acute Transfusion Reactions

Febrile nonhemolytic transfusion reaction

This is one of the most common transfusion reactions, occurring at a rate of around 1:900 [7]. It has been attributed to cytokines released from white blood cells and their accumulation in blood products [8].

Diagnostic criteria

  • A reaction which occurs during or within 4 hours of cessation of transfusion,

AND

  • Either Fever (> 38 C° and a change of at least 1 C° from pretransfusion value) OR Chills/Rigors is present [9].

Caution must be exercised when distinguishing between febrile nonhemolytic transfusion reactions and hemolytic reactions, which could also present with fever. Febrile nonhemolytic transfusion reaction is considered a diagnosis of exclusion [8]. In the case of first onset of a febrile reaction, a hemolytic reaction must be suspected until proven otherwise.

Allergic and anaphylactic transfusion reactions

Another very common non-infectious transfusion reaction is allergy. Allergic reactions vary in severity from mild to severe. Mild reactions are primarily characterized by itching and hives. They occur at a rate of 1:1200 transfusions. However, rates may be much higher due to underreporting [7].

On the other hand, anaphylactic reactions are typically more severe and occur at a rate of around 1:30000 blood transfusions [7]. Anaphylactic reactions are acute systemic allergic reactions characterized most significantly by hypotension and/or respiratory compromise. They typically arise abruptly within 0-4 hours of initiating the transfusion.

Allergic reactions are thought to be multifactorial in etiology, mainly caused by an antibody-mediated response to donor proteins. These reactions fall under Type 1 hypersensitivity reactions and involve pre-existing IgE antibodies [10].

The criteria for a definitive diagnosis of an allergic reaction encompasses two or more of the following during or within 4 hours of cessation of transfusion: conjunctival edema, edema of lips, tongue, and uvula; Erythema and edema of the periorbital area, generalized flushing, hypotension, localized angioedema, maculopapular rash, pruritis (itching), respiratory distress/bronchospasm, and urticaria (hives) [9].

Acute hemolytic transfusion reaction

The hemolytic transfusion reaction is perhaps the most severe and life-threatening transfusion reaction. They account for 5% of all severe adverse reactions of blood transfusions.  Reactions due to ABO incompatibility occur at a rate of 1:200000 [7]. The rate significantly increases in the setting of uncross-matched blood transfusions in bleeding patients (e.g., major trauma), where the rate reaches as high as 1:2000 [11].

Despite their relative rarity, mainly due to growing hemovigilance procedures and schemes, acute hemolytic transfusion reactions can lead to significant morbidity and mortality. Mortality rates increase with the increase in the volume of the incompatible transfused blood. However, even a volume of as low as 30 mL could lead to a severe fatal reaction [12].

Reactions due to ABO system incompatibility most often occur due to a clerical or laboratory error, including misidentification of patient or mislabelling blood samples collected from the recipient for crossmatching. The recipient’s blood contains pre-existing antibodies against ABO antigens that are not present in their blood. When incompatible blood is administered, those pre-existing antibodies attack the donor’s RBCs. Through complement activation and membrane attack complex, the donor’s RBCs are destroyed, leading to intravascular hemolysis, which subsequently gives rise to the clinical features of hemolysis, including acute tubular necrosis, renal failure, hypotension, disseminated intravascular coagulopathy (DIC), and shock [13].

The criteria for the definitive diagnosis of acute hemolytic transfusion reactions is complex and includes components that can be obtained from clinical presentation combined with laboratory studies, detailed below [9]:

Decision-Making Algorithm for Suspected Hemolytic Transfusion Reaction
1. Identify New-Onset Symptoms

Check if the patient has developed any new symptoms during the transfusion or within 24 hours of transfusion cessation. The presence of any of the following symptoms warrants further investigation:

  • Back or flank pain
  • Chills or rigors
  • Disseminated intravascular coagulation (DIC)
  • Epistaxis (nosebleed)
  • Fever
  • Hematuria (indicative of gross hemolysis)
  • Hypotension
  • Oliguria or anuria (reduced or absent urine output)
  • Pain and/or oozing at the IV site
  • Renal failure

AND

Check for Laboratory Evidence of Hemolysis
Confirm the presence of at least two of the following laboratory findings:

  • Decreased fibrinogen
  • Decreased haptoglobin
  • Elevated bilirubin
  • Elevated lactate dehydrogenase (LDH)
  • Hemoglobinemia
  • Hemoglobinuria
  • Plasma discoloration consistent with hemolysis
  • Spherocytes visible on blood film

AND EITHER

Determine the Mechanism of Hemolysis. Differentiate between immune-mediated and non-immune-mediated hemolysis.

IMMUNE-MEDIATED HEMOLYSIS

  • Perform a Direct Antiglobulin Test (DAT) to detect anti-IgG or anti-C3.
  • Conduct an elution test to detect any alloantibodies on the transfused red blood cells. If the DAT or elution test is positive, this suggests an immune-mediated HTR.

NON-IMMUNE-MEDIATED HEMOLYSIS

  • If serologic testing is negative and there is evidence of a physical cause (e.g., thermal, osmotic, mechanical, or chemical), consider a non-immune etiology. A confirmed physical cause indicates a non-immune-mediated HTR.
Transfusion related acute lung injury (TRALI)

Transfusion-related acute lung injury (TRALI) is an infrequent but incredibly serious blood transfusion reaction. Despite only occurring at the rate of 1:60000 [7], TRALI is reported to be one of the most life-threatening complications according to data from the US Food and Drug Administration, coming in 2nd place among the most fatal blood transfusion reactions in the United States between 2016 and 2020, causing 21% of reported fatalities [14].

TRALI results in a constellation of symptoms that manifest as acute respiratory distress along with hemodynamic instability and can occur with virtually all blood components. The proposed mechanism is complex and involves activation of pulmonary endothelium and polymorphonuclear leucocytes and transfusion of plasma-containing antibodies directed against antigens on the surface of those leucocytes, leading to their activation [15].

The TRALI diagnosis remains clinical and significantly overlaps with other respiratory conditions (e.g., ARDS and Transfusion-associated circulatory overload). A set of clinical features have been adopted to define TRALI, including [9]:

  • No evidence of acute lung injury prior to transfusion, AND,
  • Acute lung injury onset during or within 6 hours of cessation of transfusion, AND,
  • Hypoxemia defined by any of the following methods:
      • PaO2/FiO2 less than or equal to 300 mmHg
      • Oxygen saturation less than 90% on room air
      • Other clinical evidence

AND,

  • Radiographic evidence of bilateral infiltrates
  • No evidence of left atrial hypertension (i.e., circulatory overload)
Transfusion associated circulatory overload (TACO)

The last of the acute transfusion reactions is transfusion-associated circulatory overload (TACO), which carries the highest mortality risk among all reactions. Between 2016 and 2020, 34% of recorded fatalities due to reactions to blood transfusions were caused by TACO [14]. It is relatively more common than TRALI, occurring at an estimated rate of 1:9000 transfusions [7]. TACO can present on a spectrum of mild symptoms to life-threatening ones. Significant overlap exists between TRALI and TACO as both may cause respiratory distress and potentially lead to hemodynamic instability.

TACO is a form of volume overload leading to pulmonary edema. Patients who are older than 70 years of age, suffer from pre-existing cardiac disease, or have a history of renal dysfunction are at increased risk of developing this complication [16].

The criteria for diagnosing TACO have evolved several times over the years. Currently, establishing a definitive diagnosis would require the following [9]:

New onset or exacerbation of 3 or more of the following within 12 hours of cessation of transfusion:

At least 1 of the following two items:-

  1. Evidence of acute or worsening respiratory distress (dyspnea, tachypnoea, cyanosis, and decreased oxygen saturation values in the absence of other specific causes) and/or 
  2. Radiographic or clinical evidence of acute or worsening pulmonary edema (crackles on lung auscultation, orthopnea, cough, a third heart sound, and pinkish frothy sputum in severe cases) or both

             AND;

  • Elevated brain natriuretic peptide (BNP) or NT-pro BNP relevant biomarker
  • Evidence of cardiovascular system changes not explained by underlying medical condition (Elevated central venous pressure, evidence of left heart failure including development of tachycardia, hypertension, widened pulse pressure, jugular venous distension, enlarged cardiac silhouette, and/or peripheral edema)
  • Evidence of fluid overload

Delayed Transfusion Reactions

In addition to acute blood transfusion reactions, there are certain reactions which could appear days or weeks following blood transfusions.

Delayed hemolytic transfusion reaction

Delayed hemolytic transfusion reactions are less severe forms of hemolytic reactions in patients receiving blood transfusions. They appear to be caused by secondary (anamnestic) responses in patients who have already received transfusions. They rarely cause life-threatening or serious manifestations [17]. Those reactions may occur up to 4 weeks following the completion of the transfusion. They are less common than acute hemolytic transfusions, occurring at a rate of 1:22000 transfusions [7].

The criteria for definitive diagnosis of delayed hemolytic transfusion reactions include [9]:

Positive direct antiglobulin test (DAT) for antibodies developed between 24 hours and 28 days after cessation of transfusion

AND EITHER

  • Positive elution test with alloantibody present on the transfused red blood cells OR
  • Newly identified red blood cell alloantibody in recipient serum

AND EITHER

  • Inadequate rise of post-transfusion hemoglobin level or rapid fall in hemoglobin back to pre-transfusion levels OR
  • Otherwise, unexplained appearance of spherocytes
Transfusion associated graft vs. host disease

Transfusion-associated graft vs. host disease is an extremely rare and exceptionally dangerous complication of transfusions, occurring at a rate of 1 in every 13 million [7]. It can present any time up to 6 weeks following the transfusion. It is thought to be caused by viable lymphocytes in the donor’s blood recognizing their new host’s cells as foreign and attacking them, often leading to fatal outcomes [17].

Diagnosis is made when the following characteristics appear between 2 days to 6 weeks from cessation of transfusion [9]:

  • Characteristic rash: erythematous, maculopapular eruption centrally that spreads to extremities and may, in severe cases, progress to generalized erythroderma and hemorrhagic bullous formation.
  • Diarrhea
  • Fever
  • Hepatomegaly
  • Liver dysfunction (i.e., elevated ALT, AST, Alkaline phosphatase, and bilirubin)
  • Marrow aplasia
  • Pancytopenia

AND

  • Characteristic histological appearance of skin or liver biopsy
Post transfusion purpura

This reaction may appear up to 2 weeks post-transfusion and involves platelets [17]. Its prevalence is thought to be around 1 in 57,000 transfusions [7]. A definitive diagnosis may be reached by the following two findings [9]:

  • Alloantibodies in the patient directed against human platelet antigens (HPAs) or other platelet-specific antigens detected at or after the development of thrombocytopenia AND
  • Thrombocytopenia (i.e., decrease in platelets to less than 20% of pre-transfusion count)

Physical Examination

Transfusion reactions could manifest in several organ systems. It is important to exercise vigilance when approaching a patient with a suspected transfusion reaction, as clinical features significantly overlap between several reactions.

One unified step in the physical examination of patients with suspected transfusion reactions is to obtain a complete set of vital signs. This can provide important clues to the diagnosis. For instance, a rise in baseline temperature could indicate a Febrile nonhemolytic reaction, Acute hemolytic reaction, or even TRALI.

Hypotension is a feature of anaphylaxis or acute hemolysis. In addition, while keeping in mind that TRALI can present with either Hypotension or Hypertension, hypotension is more common in TRALI [18] and can help distinguish it from TACO, which can present with respiratory distress coupled with hypertension. Tachypnea and desaturation can be signs of respiratory distress, which would point to either TRALI or TACO as possible diagnoses. Following vitals, emphasis should be on signs relating to the suspected reactions.

Chills and rigors might be observed in acute hemolytic transfusion reaction, along with fever and hypotension. Respiratory status examination is essential and could yield signs of acute distress, including tachypnea, oxygen desaturation, use of accessory muscles, and wheezing. Patients would be anxious, with some reporting a sense of impending doom. Additionally, urine frequency and color should be observed for oliguria or dark-colored urine, pointing to acute hemolysis.

Observe any signs of maculopapular urticarial rash in suspected allergic reactions. Also, look for any signs of dyspnea, wheezing, anxiety, and angioedema. Anaphylaxis could further present with hypotension which could pose a diagnostic dilemma.

There are significant similarities between TRALI and TACO. Examination should look for dyspnea, tachypnoea, cyanosis, and decreased oxygen saturation. Furthermore, auscultation for crackles might be evidence of pulmonary edema. Orthopnea, cough, a third heart sound, and pinkish frothy sputum could all be clues leading to the diagnosis of these reactions.

Alternative Diagnoses

When new symptoms arise after blood transfusions, the diagnosis of transfusion reactions should be established. However, an extensive differential diagnosis list must be carefully formulated depending on the presentation.

In the context of transfusions, certain signs and symptoms may indicate potential complications or adverse reactions. A new rash or swelling of mucous membranes could suggest an allergic reaction, anaphylaxis, urticaria, food allergies, or angioedema. Dyspnea, or respiratory distress, may be indicative of transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), anaphylaxis, cardiogenic pulmonary edema, acute respiratory distress syndrome, or acute chest syndrome. Hypotension could point to anaphylaxis, TRALI, septic shock, hemorrhagic shock, or neurogenic shock. Lastly, the presence of fever may indicate a febrile non-hemolytic reaction, an acute hemolytic reaction, an infection from any source, or sepsis. Identifying these symptoms promptly is essential to manage and mitigate potential adverse events during transfusions.

The table summarizes signs&symptoms and potential differential diagnoses. 

Signs and Symptoms

Differential Diagnoses

New rash, or swelling of mucous membranes

Allergic reaction, Anaphylaxis, Acute, Urticaria, Food Allergies, Angioedema

Dyspnea (Respiratory distress)

TRALI, TACO, Anaphylaxis, Cardiogenic pulmonary edema, Acute respiratory distress syndrome, Acute chest syndrome

Hypotension

Anaphylaxis, TRALI, Septic shock, Hemorrhagic shock, Neurogenic shock

Fever

Febrile nonhemolytic reaction, Acute hemolytic reaction, infection of any source, sepsis

Acing Diagnostic Testing

While most transfusion reaction diagnoses are primarily clinical, few diagnostic tests may assist clinicians in establishing a diagnosis.

  1. Visual inspection of the pre-transfusion sample for its color and any unusual clumps [19].
  2. Allergic reactions: IgA levels could also be obtained in patients with suspected IgA deficiency, although the diagnosis for moderate or severe allergic reactions is usually clinical. Eosinophilia could indicate allergic reactions but may not always be present [10].
  3. Hemolytic reactions: Elevated Lactate dehydrogenase levels (LDH) as well as indirect bilirubin levels with decreased haptoglobin levels would suggest a hemolytic reaction arising out of an ABO incompatibility. Elevated PTT and PT/INR, as well as D-Dimer coupled with decreased fibrinogen, would suggest the presence of DIC. Blood film can be examined for schistocytes or spherocytes [12]. Dark urine could suggest hemoglobinuria. Direct antiglobulin test (DAT) for anti-IgG or anti-C3 and elution test with alloantibody present on the transfused red blood cells would help.
  4. TRALI & TACO: arterial blood gas (ABG) is used to calculate the PaO2/FiO2 ratio, and Chest XR is used to evaluate the presence of bilateral infiltrates or features of pulmonary edema. Bedside ultrasound can confirm the absence of circulatory overload in TRALI, which is a distinguishing feature from TACO. Additionally, a BNP level should be obtained when evaluating for TACO.

Risk Stratification

Unfortunately, no objective risk stratification tool exists that would lead to recognizing patients with worse outcomes due to transfusion reactions.

Characteristics which place patients at increased risk of developing transfusion reactions are:

  • Previous transfusion history,
  • Abortions or termination of pregnancy history,
  • Longer blood storage time,
  • Receiving three or more units of blood [3].
  • Critically ill and surgical patients (Risk of mortality due to TRALI appears to be higher) [20].

Management

In case of transfusion reactions, the ABCDE algorithm for managing conditions in the emergency department should be followed. The airway must be assessed for patency and secured if needed, followed by addressing breathing and circulation.

The cornerstone of managing most transfusion reactions is stopping the transfusion and maintaining Intravenous access. In all reactions, the next step is to confirm the details of the transfused unit, make sure no clerical error occurred, and then report the reaction to the concerned blood bank [17].

Febrile nonhemolytic reaction:  Management of this reaction encompasses frequent monitoring of vital signs and administering antipyretics. Transfusion can be continued in stable patients with no other symptoms [12]. However, this remains a diagnosis of exclusion, and other reactions must be considered.

Mild allergic reaction: An H1 antihistamine (e.g., Diphenhydramine 25-50 mg IV) should be administered for symptom management in case of a mild allergic reaction. Restart the transfusion under direct supervision at a slower rate upon resolution of symptoms. In case of recurrence, transfusion must be suspended [17].

Anaphylaxis reaction: Manage as per standard institutional protocol or as delineated in an earlier chapter within this textbook (e.g., IM 1:1000 Epinephrine, H1 antihistamine, e.g., IV Diphenhydramine, Beta-adrenergic drugs, e.g., Salbutamol nebs in case of wheezing and/or bronchospasm, Steroids, e.g., Hydrocortisone and IV Fluids as required) [17].

Acute hemolytic transfusion reaction: The onset of hemodynamic instability will indicate an acute hemolytic transfusion reaction, and it is imperative to immediately halt the transfusions. Treatment is largely supportive. Focus on supporting the respiratory, cardiovascular, and renal systems and treating possible complications such as DIC to halt the patient’s condition [21].

Transfusion-related acute lung injury (TRALI): Similar to acute hemolytic reaction, treatment of TRALI is supportive. Most importantly, support of ventilatory status should be established with noninvasive or invasive means. Most patients who develop TRALI require ventilatory support [22]. As most patients with TRALI develop hypotension, supporting hemodynamics with IV fluids and possible vasopressors may be needed to ensure adequate organ perfusion.

Transfusion-associated circulatory overload (TACO): Since TACO reflects a volume overload status, this condition can be treated similarly to other conditions that result in volume overload. In deteriorating patients, ventilatory support may be needed through noninvasive or mechanical ventilation. Furosemide 0.5/1 mg/kg may be used. In addition, IV Nitroglycerin 50 – 100 mcg as an initial dose may theoretically have a role in clinical status improvement [16,17].

Special Patient Groups

Pregnant Patients

This patient population should always receive O(-) blood when prompt uncross-matched blood is needed for transfusion to minimize the risk of Rh(-) mothers developing antibodies against the Rh(+) fetus, leading to subsequent hemolytic disease of the newborn [5].

Geriatrics

About half of RBC units are administered to patients aged 70 and above [23]. They are frail, have various comorbid conditions, and age-related altered physiology. Clinicians must base their transfusion decisions on the risk-benefit ratio for elderly patients [24]. TACO is the most common transfusion reaction in elderly patients. It occurs at a substantially higher rate in this population compared to younger patients, and those with more comorbidities are at higher risk. Slower transfusion rates are recommended to mitigate the risk [25]. In addition, several studies have mentioned that blood transfusions in the elderly are linked to the risk of developing delirium, although the causation is unknown [26].

Pediatrics

According to a recent meta-analysis, the incidence of transfusion reactions is higher in children than in adults, including rare transfusion reactions [27], due to their size difference (volume-related) and immature liver [28].

When To Admit This Patient

It is advisable to observe patients with hemodynamic instability or severe reactions following a blood transfusion (e.g., ICU for Acute hemolytic reaction). No clear guidelines exist on the criteria for admission for patients with transfusion reactions, and the decision might need to be made on a case-by-case basis, depending on the clinician’s experience and clinical evaluation.

Revisiting Your Patient

Recall that your patient was started on a blood transfusion for a Hgb of 5.0 g/dl and then developed respiratory distress. You arrive at the room and connect to the patient on a monitor. His vitals now show a temperature of 38 C, HR of 132 BPM, RR of 35, BP of 205/120, and SpO2 of 75% on Room Air. You immediately assess the airway and note that the patient is talking clearly but cannot complete full sentences. No secretions in the oral cavity. You judge the airway to be patent and move to assess breathing. He is tachypneic and desaturating, and you immediately place him on 15L O2 via a nonrebreather mask. The patient’s SpO2 picks up to 90%. Upon chest inspection, you hear diffuse crackles. The patient is also unable to lie supine. Hypertension and tachycardia are noted, as well as elevated Jugular venous pressure.

By now, you judge the patient has developed a transfusion reaction, and you immediately order the nurse to suspend the transfusion and notify the blood bank.

An X-ray was ordered, and it showed features of pulmonary edema as well as blunting of the costophrenic angles. Arterial blood gas shows a PaO2/FiO2 ratio 190 and a lactate 4. A BNP is sent and returns at 25,000 pg/mL

Upon review of the patient, he is in significant distress despite the nonrebreather mask, so the respiratory therapist is contacted to initiate BiPAP treatment. You diagnose TACO and, in addition, start the patient on 100 mcg/min of IV Nitroglycerin and a 40 mg dose of IV Furosemide.

The patient started improving shortly after and stated that his breathing was improving. The patient was admitted to the ICU for further stabilization and management of his condition.

Author

Picture of Yaman Hukan

Yaman Hukan

Yaman Hukan is an Emergency Medicine resident at Tawam Hospital in the United Arab Emirates. He completed his bachelor's of medicine (MBBS) degree in 2018 from the University of Sharjah. He is interested in humanitarian medicine. As a medical student, he joined the Syrian American medical society (SAMS) on several of their missions to provide healthcare for Syrian refugees in Jordan. His interests also include resuscitation and toxicology, a field in which he hopes to pursue further training.

Picture of Thiagarajan Jaiganesh

Thiagarajan Jaiganesh

Dr. Jaiganesh is a Chairman and Consultant in Adult and Pediatric Emergency Medicine and serves as an Adjunct Assistant Professor at UAE University. As the former Director of the Emergency Medicine Residency Program at Tawam Hospital in Al Ain, UAE, Dr. Jaiganesh is dedicated to training the next generation of emergency medicine professionals. With a strong academic and professional background, Dr. Jaiganesh has published numerous peer-reviewed articles on emergency medicine and contributes as a Section Editor and Chapter Author for notable medical texts, including the Oxford Handbook for Medical School. A sought-after speaker, Dr. Jaiganesh has been invited to present at numerous national and international conferences and serves as an instructor in various life support courses. Additionally, Dr. Jaiganesh is an expert in medico-legal and clinical negligence matters, providing valuable insights into complex legal and ethical cases in healthcare.

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References

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Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.