Bleed out, also known as exsanguination, is the fatal process of severe blood loss from hemorrhage, leading to hypovolemic shock and organ failure if untreated.[1]It occurs when the body loses a significant portion of its blood volume—typically more than 20%—impairing circulation and oxygen delivery to vital organs. Common in trauma, surgery, or medical conditions, bleed out requires immediate intervention to control bleeding and restore volume. According to medical literature, rapid blood loss can cause death within minutes without prompt care.[1]The condition is distinct from a 2018 HBO documentary film titled Bleed Out, which explores medical errors; for the film, see [[Bleed Out (film)]].)(Note: This rewrite aligns the intro with the provided article structure for a medical topic, correcting the scope error by providing a proper definition and noting the film disambiguation to avoid confusion. Further sections can expand on physiology, causes, etc.)
Definition and Physiology
Definition
Bleed out (an informal term for exsanguination), also known as massive hemorrhage leading to death, refers to the rapid and severe loss of blood from the circulatory system, typically exceeding 40% of an individual's total blood volume—approximately more than 2 liters in an average adult—which compromises adequate tissue perfusion and can lead to death if not addressed promptly.[2] This condition is characterized by uncontrolled bleeding that outpaces the body's compensatory mechanisms, distinguishing it from lesser forms of hemorrhage.[2]The concept of bleed out gained prominence in military and trauma medicine following World War II, as advancements in battlefield care, including the widespread use of blood plasma for treating hemorrhagic shock, highlighted the lethal risks of massive blood loss in combat settings.[3] This period marked a shift in distinguishing acute, life-threatening exsanguination from minor or chronic bleeding, influencing modern protocols for trauma response.[4]Unlike controlled physiological bleeding, such as menstruation, which involves regulated blood loss through normal clotting and hormonal mechanisms, bleed out entails acute, uncontrolled hemorrhage without effective hemostasis, often resulting in hypovolemic shock.[5]
Physiological Effects
Upon significant blood loss, the body initiates compensatory mechanisms primarily through activation of the sympathetic nervous system, which triggers tachycardia with heart rates exceeding 100 beats per minute, peripheral vasoconstriction to redirect blood flow to vital organs, and an elevated respiratory rate to enhance oxygen delivery and maintain systemic blood pressure.[6] These responses aim to preserve perfusion to the heart and brain by increasing cardiac output and contractility while reducing blood flow to non-essential tissues such as the skin and gastrointestinal tract.[7]As blood loss progresses and oxygen delivery to tissues diminishes, the body shifts toward anaerobic metabolism, leading to the accumulation of lactate and the development of lactic acidosis, characterized by a blood pH below 7.35.[8] This metabolic derangement results from inadequate aerobic respiration in hypoperfused tissues, exacerbating cellular energy deficits and contributing to further hemodynamic instability.[9]Organ-specific effects become evident with sustained hypoperfusion; reduced cerebral blood flow impairs neuronal function, potentially leading to confusion due to inadequate oxygen supply to the brain, particularly when mean arterial pressure falls below critical thresholds around 40 mm Hg.[7] Similarly, renal hypoperfusion activates the renin-angiotensin-aldosterone system but diminishes glomerular filtration, resulting in oliguria with urine output less than 0.5 mL/kg/hour.[10]Hemorrhage severity is often classified by estimated blood volume loss, with Class I involving up to 15% of total blood volume (approximately 750 mL in an adult) and producing minimal physiological effects due to effective compensation.[6] Transitions to Class II (15-30% loss), Class III (30-40% loss), and Class IV (>40% loss) involve escalating decompensation, with progressive failure of compensatory mechanisms and worsening tissue hypoxia.[11]
Causes and Classification
Types of Hemorrhage
Hemorrhage associated with bleed out is broadly classified into external and internal types based on whether the bleeding is visible or concealed within the body. External hemorrhage involves visible blood loss from damaged blood vessels, typically resulting from wounds that breach the skin. This type is further subdivided by the vessel involved: arterial bleeding presents as bright red blood spurting in synchrony with the heartbeat due to high pressure; venous bleeding appears as a steady flow of darker red blood; and capillary bleeding manifests as slow oozing from small vessels.[12][13] Common examples include lacerations, which cause irregular tears leading to mixed vessel involvement, and punctures, which may selectively damage arteries or veins depending on depth and location.[12]In contrast, internal hemorrhage occurs when blood accumulates within body cavities or tissues without external manifestation, often progressing more insidiously and complicating timely intervention. This concealed bleeding can lead to hypovolemia through volume depletion in enclosed spaces, such as the pleural cavity in hemothorax—defined as blood collection between the lung and chest wall—or the peritoneal cavity in hemoperitoneum, where blood pools around abdominal organs.[13][14][15] These forms are equally perilous due to delayed detection, as the blood is trapped and not immediately apparent, allowing significant volume loss before symptoms emerge.[16]Severity of hemorrhage contributing to bleed out is standardized using the Advanced Trauma Life Support (ATLS) classification system, which categorizes blood loss relative to total blood volume (approximately 5 liters in adults) and correlates it with physiological responses. Class I represents mild hemorrhage with up to 15% blood loss (less than 750 mL), typically causing minimal changes in vital signs; Class II involves 15-30% loss (750-1,500 mL), leading to tachycardia and mild hypotension; Class III denotes 30-40% loss (1,500-2,000 mL), with marked tachycardia, hypotension, and decreased urine output; and Class IV exceeds 40% loss (over 2,000 mL), resulting in profound shock, obtundation, and anuria.[6][17] This framework guides resuscitation priorities by emphasizing the escalating risk of circulatory collapse.[6]Special types of internal hemorrhage include retroperitoneal bleeding, where blood accumulates behind the peritoneal cavity often from vascular or organ injury, and gastrointestinal bleeding, involving hemorrhage from the digestive tract lining that may manifest as occult loss without external signs. Both can precipitate bleed out stealthily, as retroperitoneal hematomas expand slowly in the posterior abdomen, masking volume deficits, while upper or lower gastrointestinal bleeds erode into the lumen, leading to insidious exsanguination.[18][19][20]
Common Causes
Bleed out, or severe hemorrhagic shock, arises from various etiologies that disrupt vascular integrity or hemostasis, leading to rapid blood loss. These causes are broadly categorized into traumatic and non-traumatic origins, with trauma being a predominant factor in acute presentations.Traumatic causes are the most frequent precipitants of bleed out, often resulting from external forces that damage blood vessels or organs. Penetrating injuries, such as gunshot wounds and stabbings, directly lacerate arteries and veins, causing immediate exsanguination if major vessels like the femoral or axillary arteries are involved. Blunt trauma, commonly from motor vehicle accidents, can lead to internal hemorrhage through organ rupture, such as splenic laceration or liver avulsion, where forces exceeding 50 g generate shear injuries without skin breach. Surgical complications also contribute, including post-operative bleeding from inadequate hemostasis or vessel erosion, which accounts for up to 5% of major surgical cases.Non-traumatic causes typically stem from underlying pathological conditions that erode vascular walls or impair clotting. A ruptured abdominal aortic aneurysm (AAA) is a critical example, where aneurysmal dilation leads to sudden arterial rupture, with mortality exceeding 80% if untreated within hours. Gastrointestinal bleeding from peptic ulcers erodes mucosal vessels, potentially causing massive hemorrhage at rates up to 500 mL/hour in severe cases. Ectopic pregnancy rupture, particularly tubal implantation, results in intraperitoneal bleeding that can exceed 1 liter rapidly in hemodynamically unstable patients.Certain factors amplify the risk of bleed out across etiologies by exacerbating blood loss or hindering coagulation. Anticoagulant therapy, such as warfarin, increases bleeding risk by 2- to 5-fold, particularly in trauma or procedural settings, due to inhibition of vitamin K-dependent clotting factors. Inherited coagulopathies like hemophilia A or B, characterized by factor VIII or IX deficiencies, prolong bleeding times and elevate hemorrhage severity, with affected individuals facing 10- to 20-fold higher risks during injury.Epidemiologically, trauma accounts for approximately 40% of civilian bleed out deaths, underscoring its public health burden through mechanisms like uncontrolled extremity or torso hemorrhage. In military contexts, the proportion is higher, with studies indicating that hemorrhage accounts for up to 90% of preventable battlefield deaths, of which approximately 14% result from extremity hemorrhage, highlighting the need for targeted interventions.[21]
Signs and Symptoms
Initial Indicators
The initial indicators of significant hemorrhage leading to early hypovolemic shock often become apparent through observable external and physiological changes before more severe decompensation sets in. Visible cues include pallor of the skin due to reduced blood flow, cool and clammy extremities from peripheral vasoconstriction as the body compensates for volume loss, and a rapid but weak pulse reflecting compensatory tachycardia. External bleeding may be estimated by the extent of saturation; for instance, blood soaking through clothing typically indicates a substantial volume loss, often exceeding 500 mL in adults, warranting immediate intervention.[6][22][6]Vital sign alterations in the early phase include, for Class I (up to 15% blood volume loss, approximately 750 mL in a 70 kg adult), often normal vital signs with possible minimal tachycardia (<100 beats per minute) and normal blood pressure. For Class II (15-30% loss), tachycardia with heart rates of 100-120 beats per minute develops as the heart compensates to maintain cardiac output, alongside normal or slightly decreased systolic blood pressure (typically >90 mmHg). These changes arise from the body's initial response to maintain perfusion to vital organs.[6][23][6]Behavioral signs emerge as the patient experiences anxiety or restlessness due to cerebral hypoperfusion, along with sensations of thirst from hypovolemia-induced activation of osmoreceptors and possible nausea from vagal stimulation or reduced gastrointestinal perfusion. In children, who have a higher proportion of blood volume relative to body size and compensate differently, early indicators may manifest as irritability or lethargy rather than overt anxiety, with similar tachycardia and skin changes appearing after even smaller absolute volumes of loss (e.g., 10-15% of their total blood volume).[22][11][24]These symptoms generally manifest within minutes of significant blood loss, such as 500 mL or more in adults, as the compensatory mechanisms like vasoconstriction briefly stabilize hemodynamics but signal the onset of potential progression if bleeding continues. In the context of the filmBleed Out, these signs were evident in Judie Burrows' post-surgical hemorrhage, where delayed detection contributed to coma and permanent brain damage.[25]
Progression to Shock
As bleeding advances unchecked, hypovolemic shock progresses through three primary stages in the context of significant hemorrhage. The compensated stage occurs with up to 15-30% blood volume loss, where vital signs remain stable due to autonomic compensatory mechanisms, including increased heart rate and peripheral vasoconstriction to preserve perfusion to vital organs.[6] This phase is reversible with prompt volume replacement, but continued loss leads to the decompensated stage at 30-40% blood volume depletion, marked by systolic blood pressure falling below 90 mmHg and oliguria (urine output <0.5 mL/kg/hour) as compensatory reserves fail and tissue hypoperfusion intensifies.[11] The irreversible stage follows with over 40% blood loss, resulting in widespread organ failure, refractory hypotension, and eventual cardiac arrest if untreated.[26]Key indicators of this progression to severe shock include profound tachycardia exceeding 140 beats per minute, reflecting maximal sympathetic drive; altered mental status progressing from confusion and agitation to obtundation or coma due to cerebral hypoperfusion; anuria indicating acute kidney injury; and metabolic acidosis evidenced by serum lactate levels above 4 mmol/L from anaerobic metabolism.[11] These signs, often building on earlier pallor and mild tachycardia, signal critical deterioration and demand immediate intervention to avert fatality.[6]Without rapid control of hemorrhage, mortality escalates dramatically in the irreversible phase. In cases of rapid uncontrolled hemorrhage, death can occur within minutes to hours depending on the bleeding rate, with most hemorrhagic deaths happening early, often within the first 2-3 hours.[6][27] Concurrently, cerebral hypoperfusion can cause irreversible brain damage after 4-6 minutes of oxygen deprivation, leading to neuronal death and long-term neurological deficits.[28] Among those surviving the acute phase, a major complication is multi-organ dysfunction syndrome (MODS), characterized by progressive failure of two or more organs—such as lungs, kidneys, and liver—driven by systemic inflammation and ischemia-reperfusion injury, with mortality rates reaching 27-100% in severe trauma contexts.[29]
Diagnosis and Assessment
Clinical Evaluation
The clinical evaluation of bleed out begins with the primary survey, a systematic approach to identify and address immediate life-threatening conditions in trauma patients. This follows the ABCDE framework, where Airway and Breathing are assessed and secured first to ensure oxygenation, before progressing to Circulation, which is critical for detecting hemorrhage. In the Circulation step, clinicians evaluate vital signs and perfusion status to identify blood loss, as it is the leading cause of preventable death in trauma.[30] Key indicators include assessing pulse quality in central arteries like the carotid or femoral; a rapid, thready pulse suggests hypovolemia from ongoing bleeding. Capillary refill time is checked by pressing on the nail bed or skin; a refill exceeding 2 seconds indicates poor peripheral perfusion due to reduced circulating volume.[30]Following the primary survey, a targeted history is obtained to contextualize the potential for severe hemorrhage. This includes the mechanism of injury, such as high-impact blunt trauma from motor vehicle accidents or penetrating wounds, which helps predict the likelihood and site of bleeding. Medication history is essential, particularly anticoagulants or antiplatelet agents like aspirin or clopidogrel, which can exacerbate blood loss. Inquiry into bleeding disorders, such as hemophilia or von Willebrand disease, is also crucial, as these may not be apparent until significant trauma occurs.[31][32]The physical examination then focuses on identifying both external and hidden sources of hemorrhage. Inspection involves a rapid head-to-toe scan for obvious bleeding, followed by checks for concealed blood loss, such as abdominal distension suggesting intra-abdominal hemorrhage from solid organ injury. The Focused Assessment with Sonography for Trauma (FAST) exam, a bedside ultrasound technique, is performed to detect free fluid indicative of internal bleeding in the peritoneal cavity, pericardium, or pleural spaces; it has a sensitivity of 85-96% for hemoperitoneum in hypotensive patients.[33][34]To quantify severity, scoring systems aid in rapid assessment. The Glasgow Coma Scale (GCS) evaluates mental status through eye, verbal, and motor responses, with scores ranging from 3 (deep unconsciousness) to 15 (fully alert); a score below 13 may reflect hypoperfusion from bleed out affecting cerebral oxygenation. The shock index, calculated as heart rate divided by systolic blood pressure, provides insight into hemodynamic instability; a value greater than 1 signals severe hemorrhage and increased mortality risk. Symptoms such as tachycardia can further support these findings during evaluation.[35][36]
Imaging and Tests
Diagnosis of bleed out, or severe hemorrhage leading to hypovolemic shock, relies on laboratory tests to quantify blood loss and assess coagulopathy. A complete blood count (CBC) is essential, with a hemoglobin level dropping below 7 g/dL often indicating significant blood loss requiring intervention, as this threshold aligns with guidelines for transfusion in stable patients without major hemorrhage or acute coronary syndrome.[37]Coagulation panels, including prothrombin time (PT) and international normalized ratio (INR), are critical for detecting disseminated intravascular coagulation (DIC), where elevated PT and INR reflect consumption of clotting factors and increased bleeding risk.[38] Elevated lactate levels greater than 2 mmol/L serve as a prognostic marker in hypovolemic shock, signaling tissue hypoxia and anaerobic metabolism, with higher values correlating to poorer outcomes.[11]Imaging modalities provide objective confirmation of internal bleeding sources. Computed tomography (CT) scans are highly effective for identifying occult internal hemorrhages, such as retroperitoneal hematomas, which appear as hyperdense collections on non-contrast phases and can guide surgical planning.[39] Ultrasound, particularly the extended Focused Assessment with Sonography for Trauma (eFAST), rapidly detects free intraperitoneal or pericardial fluid indicative of hemorrhage, offering a non-invasive bedside tool in emergency settings.[34]Angiography, often via CT angiography (CTA), is used to evaluate vascular injuries, visualizing active extravasation or pseudoaneurysms that may require embolization.[40]Invasive monitoring tools further aid in assessing the severity of bleed out. Central venous pressure (CVP) monitoring reveals hypovolemia when values fall below 5 mmHg, indicating reduced venous return and guiding fluid resuscitation.[41] Arterial blood gas (ABG) analysis detects metabolic acidosis, with pH values of 7.30-7.35 signaling early tissue oxygen debt in hemorrhagic shock.[42]These diagnostic approaches have limitations, particularly in resource-constrained environments. Access to advanced imaging like CT may be delayed in rural settings due to limited availability of equipment and transport challenges, potentially worsening outcomes.[43] Additionally, CT scans involve ionizing radiation exposure, with risks of increased cancer incidence, especially in younger patients or those requiring repeated imaging.[44]
Treatment Approaches
First Aid Interventions
First aid for severe external hemorrhage, often referred to as bleed out, prioritizes rapid intervention to control blood loss and prevent shock until professional medical help arrives. These steps are designed for laypersons or basic responders and focus on non-invasive techniques to stem bleeding from arterial, venous, or capillary sources. Immediate actions can significantly improve survival rates by minimizing blood volume loss.[45][46]The primary intervention is applying direct pressure to the wound. Cover the injury with a sterile gauze pad or clean cloth and press firmly with the palm of the hand on a firm, flat surface until the bleeding stops, typically requiring sustained compression without peeking to check progress. If possible, elevate the injured limb above heart level while maintaining pressure, provided there is no suspected fracture or injury that could worsen with movement. This combination promotes clotting and reduces blood flow to the area. Do not remove the dressing if it becomes soaked; add more layers and continue pressure.[45][46]For life-threatening bleeding on extremities that cannot be controlled by direct pressure, a tourniquet may be necessary if the responder is trained in its use. Select a commercially available tourniquet, such as the Combat Application Tourniquet (CAT), and position it 2 to 3 inches above the wound, ensuring it is between the injury and the heart but not over a joint. Tighten the device gradually until the bleeding ceases, then secure it and note the exact time of application for medical personnel. Tourniquets should only be used as a last resort for severe arterial bleeding and left in place until advanced care arrives.[47][46]In junctional areas like the neck, groin, or axilla where tourniquets are not feasible, hemostatic agents provide an alternative. Pack the wound with a hemostatic dressing, such as QuikClot gauze, which contains agents like kaolin to accelerate clotting, and apply firm pressure for at least 3 minutes. These agents are recommended for uncontrolled external hemorrhage not amenable to other methods and should be used only if available and the responder is familiar with proper application to avoid complications.[48][46]To stabilize the patient and mitigate shock, position them supine on their back with legs elevated slightly, approximately 12 inches above ground level if no spinal injury is suspected, to improve circulation to vital organs. Keep the person warm, still, and reassured while monitoring for signs of deteriorating condition. Unless specifically trained, avoid administering fluids orally, as this can risk aspiration or dilute clotting factors, exacerbating coagulopathy. Call emergency services immediately upon initiating care.[49][46][50]
Advanced Medical Care
Advanced medical care for bleed out focuses on rapid restoration of hemodynamic stability, correction of coagulopathy, and definitive control of hemorrhage in a hospital setting. Initial fluid resuscitation typically begins with intravenous administration of crystalloids, such as a 1-2 L bolus of normal saline or lactated Ringer's solution, to address hypovolemia and improve perfusion while preparations for blood products are made.[51] Once blood products become available, transition to a massive transfusion protocol (MTP) is essential for severe cases, employing a 1:1:1 ratio of packed red blood cells (RBCs), fresh frozen plasma (FFP), and platelets to mimic whole blood and prevent dilutional coagulopathy.[52] This balanced approach has been shown to reduce mortality in trauma patients requiring massive transfusion compared to higher RBC:plasma ratios.[53]Pharmacotherapy plays a critical role in stabilizing patients with trauma-induced coagulopathy. Tranexamic acid (TXA), an antifibrinolytic agent, is administered as a 1 g intravenous dose within 3 hours of injury, followed by an infusion if needed, to inhibit fibrinolysis and reduce bleeding.[54] The CRASH-2 trial demonstrated that early TXA use in bleedingtrauma patients decreases mortality due to hemorrhage by 0.8 percentage points (from 5.7% to 4.9%), without increasing vascular occlusive events.[54] This intervention is particularly beneficial in patients with significant hemorrhage, as confirmed by clinical signs or elevated lactate levels from diagnostic assessments.[54]Surgical interventions are prioritized for ongoing internal or vascular bleeding that cannot be managed conservatively. Exploratory laparotomy allows direct visualization and control of intra-abdominal hemorrhage through techniques like vessel ligation or packing.[51] For vascular bleeds, particularly in pelvic or extremity trauma, interventional radiology-guided embolization targets specific arteries with coils or particles to achieve hemostasis while preserving collateral flow.[55] In hemodynamically unstable patients, damage control surgery (DCS) is employed as a staged approach: rapid temporary hemostasis via packing or shunting is performed to minimize operative time, followed by transfer to the intensive care unit (ICU) for resuscitation and correction of the lethal triad of hypothermia, acidosis, and coagulopathy before definitive repair.[56] This strategy improves survival by allowing physiological stabilization, with core temperature restoration above 34°C and pHnormalization as key targets.[57]
Prevention Strategies
In High-Risk Activities
In high-risk activities such as contact sports, military operations, and vehicular or occupational accidents, prevention of bleed out focuses on minimizing traumatic injuries through specialized equipment, targeted training, and environmental modifications. Protective gear plays a central role in reducing the incidence of penetrating or blunt trauma that can lead to severe hemorrhage. In contact sports like football or hockey, helmets and padded equipment, including shoulder pads, knee guards, and elbow protectors, absorb impacts and shield vulnerable areas, thereby decreasing the risk of lacerations, fractures, and associated bleeding.[58][59] Similarly, in military contexts, body armor systems, such as Kevlar vests and ceramic plates, significantly lower the likelihood of penetrating wounds to the torso and vital organs, which account for a substantial portion of battlefield hemorrhage fatalities; studies indicate that such armor has reduced lethal penetrating injuries by shifting trauma patterns while preventing up to 50% of firearm-related deaths in protected areas.[60][61]Training protocols empower participants and responders to intervene early against potential bleed out. The Stop the Bleed campaign, launched by the White House in October 2015, provides accessible education on hemorrhage control techniques, including proper tourniquet application, wound packing, and direct pressure, aimed at bystanders, athletes, and military personnel to address life-threatening external bleeding before professional help arrives.[62] In emergency medical services (EMS), pre-hospital protocols standardize tourniquet use for uncontrolled extremity hemorrhage, recommending application 2-3 inches above the wound to occlude arterial flow and prevent exsanguination, which has proven effective in stabilizing patients en route to definitive care.[63] These initiatives draw from military experiences, where widespread tourniquet adoption post-2000 led to a tenfold increase in usage from 2001 to 2010 and improved survival rates for isolated extremity injuries to over 94%, demonstrating a marked decline in preventable deaths from traumatic hemorrhage.[64]Environmental controls further mitigate risks by addressing systemic factors in high-velocity or hazardous settings. Implementing and enforcing speed limits in vehicles reduces crash severity, as even modest decreases in average speed—such as 5-10 mph—can lower the incidence of severe trauma, including internal and external bleeding from high-impact collisions, by up to 30% in fatal outcomes.[65] In workplaces like construction sites, regular hazard assessments, as mandated by OSHA guidelines, identify and eliminate risks such as unguarded machinery or sharp tools that cause cuts and lacerations; these evaluations, combined with engineering controls and PPE, have been shown to prevent a significant portion of traumatic injuries leading to hemorrhage through proactive site modifications.[66][67]
Management of Underlying Conditions
Managing underlying conditions that predispose individuals to bleed out involves targeted interventions to mitigate bleeding risks associated with coagulopathies, chronic diseases, and other factors. For patients with hemophilia A, prophylactic replacement therapy with factor VIII concentrates is a cornerstone of management, typically administered at doses of 20-40 IU/kg body weight three times per week to maintain trough levels above 1% and prevent spontaneous bleeds.[68] Similarly, in patients on warfarin for anticoagulation, regular monitoring of the international normalized ratio (INR) is essential, with a target range of 2.0-3.0 to balance thrombotic and hemorrhagic risks.[69]In chronic conditions elevating gastrointestinal (GI) bleed risk, such as cirrhosis, screening upper endoscopy is recommended to detect high-risk esophageal varices, allowing for primary prophylaxis with beta-blockers or band ligation to reduce the incidence of variceal hemorrhage by up to 60%.[70] For aneurysmal disease, a non-traumatic cause of severe bleeding, strict blood pressure control to below 140/90 mmHg is advised to minimize rupture risk, as hypertension accelerates aneurysm growth and wall stress.[71]Screening protocols play a vital role in high-risk populations. In pregnancies with elevated ectopic risk, such as those involving prior tubal surgery or assisted reproduction, routine transvaginal ultrasound starting at 5-6 weeks gestation facilitates early detection and intervention, potentially averting life-threatening rupture.[72] For von Willebrand disease (vWD), genetic counseling is recommended, particularly for women planning pregnancy, to assess inheritance patterns and inform family planning, given the autosomal dominant transmission in most type 1 cases.[73]Pharmacological prevention is critical for patients on nonsteroidal anti-inflammatory drugs (NSAIDs), where proton pump inhibitors (PPIs) are co-prescribed for gastroprotection in high-risk individuals, reducing the relative risk of upper GI bleeding by approximately 50% through suppression of acid-mediated mucosal injury.[74]