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53 A Comprehensive Review of Hemorrhage Pathophysiology, Classification, and Neurosurgical Management
Authors :
Syed Ali Abbas Rahat
Md Yakub
Pavithra Surulivel
Shaikh Izdan Shaikh Irfan
Awes Majid Shaikh
Toseem raja
( 1, Teacher, International Medical Faculty , Osh State University, Osh, Kyrgyzstan
2,3,4,5,6 Student, International Medical Faculty, Osh State University, Osh, Kyrgyzstan)
Hemorrhage, defined as the acute escape of circulating blood from compromised blood vessels, remains a preeminent challenge in emergency medicine and a leading cause of preventable mortality globally.1 Effective management is dictated by prompt classification, typically utilizing the Advanced Trauma Life Support (ATLS) staging system, which correlates clinical signs with estimated blood volume loss. The pathophysiology of critical bleeding transitions rapidly into hemorrhagic shock, characterized by flow-dependent oxygen consumption and the self-perpetuating cycle known as the "Lethal Diamond" (hypothermia, acidosis, coagulopathy, and hypocalcemia).3 Modern therapeutic protocols have shifted dramatically from crystalloid-heavy resuscitation to Damage Control Resuscitation (DCR), which mandates immediate hemorrhage control, permissive hypotension in select patients, and the activation of Massive Transfusion Protocols (MTPs) featuring balanced blood product ratios (1:1:1).5 Diagnosis relies on rapid bedside imaging, such as Focused Assessment with Sonography in Trauma (FAST), and increasingly, on real-time functional hemostatic assessment provided by viscoelastic testing (TEG/ROTEM).4 Specialized interventions, including Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for non-compressible torso hemorrhage and evidence-based protocols endorsed by the World Health Organization (WHO) for Postpartum Hemorrhage (PPH), reflect a commitment to highly targeted and time-sensitive care aimed at improving patient outcomes.
Hemorrhagic Shock, ATLS Classification, Damage Control Resuscitation, Massive Transfusion Protocol, Coagulopathy, Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), Tranexamic Acid, Postpartum Hemorrhage (PPH), Intracranial Hemorrhage, Neurosurgery.
Hemorrhage, or bleeding, represents the acute loss of circulating blood from disrupted vasculature.1 Depending on the severity and location of the vascular damage, blood loss can range in consequence from a trivial event to a rapidly fatal one, with death caused by excessive blood loss referred to as exsanguination.1 The immediate clinical consequence of significant hemorrhage is hypovolemia—a massive decrease in circulating blood volume—which, in turn, is the primary driver of hemorrhagic shock.8 Hemorrhage can be induced by external physical trauma or internal physiological disorders.1
Hemorrhage remains a critical, high-morbidity condition globally, especially in contexts such as severe trauma and obstetrics.2 Historical management focusing heavily on non-specific crystalloid volume replacement has been largely superseded by a strategy centered on hemostatic resuscitation.5 This approach, termed Damage Control Resuscitation (DCR), reflects a crucial evolution in emergency care, integrating rapid definitive control, targeted fluid administration, and specific blood product replacement guided by real-time physiological data.6 This review consolidates the contemporary guidelines and principles derived from international professional organizations and peer-reviewed literature, establishing the current expert standard of care.
Intracranial Hemorrhage (ICH) refers to bleeding within the skull and is divided into four primary types based on their location relative to the brain parenchyma, categorized as either extra-axial (outside the brain tissue) or intra-axial (within the brain tissue):
2.1.1 Extra-Axial Hemorrhages
1. Epidural Hemorrhage (EDH): An EDH typically occurs between the inner table of the skull and the dura mater. Classically, arterial EDH results from blunt trauma to the temporal region, often leading to a skull fracture and damage to the underlying middle meningeal artery. EDH is frequently associated with an initial lucid interval followed by rapid neurological decline due to hematoma expansion and mass effect.
2. Subdural Hemorrhage (SDH): SDH occurs beneath the dura mater, typically resulting from the tearing of bridging veins that cross the subdural space, usually due to rapid acceleration/deceleration forces. While overwhelmingly associated with head trauma, spontaneous SDH has been described in patients with existing coagulopathies or those receiving anticoagulation therapy.9
2.1.2 Intra-Axial Hemorrhages
3. Intraparenchymal Hemorrhage (IPH) / Intracerebral Hemorrhage (ICH): This involves sudden bleeding directly into the brain tissues (parenchyma) or ventricles, often referred to as a hemorrhagic stroke. Etiologies are diverse, including trauma, chronic hypertension, cerebral amyloid angiopathy (CAA), ruptured aneurysms, arteriovenous malformations (AVMs), brain tumors, and hemorrhagic transformation of an ischemic stroke.
4. Subarachnoid Hemorrhage (SAH): SAH is characterized by the presence of blood within the subarachnoid space.8 While trauma is a cause, the medical use of the term typically refers to non-traumatic bleeding, usually from the rupture of a berry aneurysm or arteriovenous malformation (AVM).8
Hemorrhage is broadly classified into two major etiological categories: traumatic and non-traumatic (spontaneous).
Traumatic Hemorrhage (TICH): This accounts for the majority of severe bleeding managed in trauma centers, especially extra-axial hemorrhages.1 Analysis of patients with isolated intracerebral hemorrhage (ICH) reveals that patients with TICH typically have a much better prognosis than those with spontaneous ICH (SICH), achieving favorable outcomes in 67% of cases, compared to 24% for SICH patients.10
Spontaneous/Non-Traumatic Hemorrhage (SICH): SICH comprises 10–15% of all strokes and is associated with high morbidity and mortality.11 The primary risk factors include chronic hypertension, which compromises vascular integrity, cerebral amyloid angiopathy (CAA), and the use of anticoagulant or antiplatelet medications.9 Less common causes include vascular malformations, hemorrhagic transformation following an ischemic stroke, brain tumors, and systemic coagulopathy disorders.9
Definitive treatment for intracranial hemorrhage often involves evacuation of the hematoma and surgical control of the bleeding source. Management strategies are highly dependent on the hematoma type, volume, patient's neurological status (Glasgow Coma Scale/GCS), and the presence of midline shift (MLS).
The decision for surgical intervention is guided by strict radiological and clinical criteria:
Management of ICH primarily focuses on aggressively controlling blood pressure, reversing coagulopathy, and managing secondary injury. Surgical intervention aims to rapidly remove the blood clot and restrain edema while limiting further neuronal damage due to the procedure.
● Surgical Intervention: ICH management ranges from aggressive medical therapy, including anti-edema measures and placement of a ventricular drain (EVD) to manage acute hydrocephalus, to open surgery for hematoma evacuation.
● Minimally Invasive Techniques: Minimally invasive surgery (MIS) approaches have emerged as an option for ICH evacuation, offering potential benefits by limiting the invasiveness of traditional craniotomy. However, the results of rigorous clinical trials assessing the efficacy of MIS methods for ICH remain mixed.
Aneurysmal SAH management is a neurosurgical emergency, focused on aneurysm obliteration and complication prevention.
● Aneurysm Treatment: Prompt evaluation and definitive treatment of the ruptured aneurysm are recommended, preferably within 24 hours of the hemorrhage. The goal is complete obliteration of the aneurysm to prevent rebleeding.
○ Treatment modality—either open surgical clipping or endovascular coiling—is determined by specialized neurovascular teams based on patient characteristics and aneurysm anatomy.
● Preventing Delayed Cerebral Ischemia (DCI): DCI, often caused by vasospasm, is a significant complication.
○ Nimodipine: Early initiation of enteral nimodipine is beneficial in preventing DCI and improving functional outcomes.
○ Hemodynamics: Maintaining euvolemia and managing blood pressure to minimize variability are important.
To standardize the assessment of acute blood loss and guide initial management, the Advanced Trauma Life Support (ATLS) curriculum provides a four-class physiological classification based on estimated blood volume loss (assuming an average adult volume of 5 liters).1 This staging system correlates quantitative blood loss with observable changes in key physiological parameters.13
Table 1: ATLS Classification of Hemorrhagic Shock (Adult)
Class I hemorrhage, involving the loss of up to 15% of total blood volume, is typically well-tolerated with few physical symptoms due to robust compensatory mechanisms.1 The transition to Class III (30–40% loss) represents a failure of compensation, marked by the onset of hypotension and significant central nervous system deterioration (confusion or combativeness).13 This critical stage necessitates immediate, aggressive resuscitation, including blood transfusion.13
Hemorrhagic shock occurs when acute blood loss results in a systemic state of inadequate cellular energy production.14 Physiologically, this condition is defined by a critical reduction in global oxygen delivery (DO2).3 When DO2 falls below a critical threshold (DO2 CRIT), oxygen consumption (VO2) becomes flow-dependent, forcing cellular metabolism into anaerobic pathways and leading to acidosis, organ damage, and potential death.3
Uncontrolled hemorrhage rapidly triggers a detrimental physiological spiral that severely impairs the body’s ability to clot. Originally the "lethal triad" (hypothermia, acidosis, and coagulopathy), modern trauma research recognizes the critical role of a fourth factor, expanding the concept to the "lethal diamond".4 Correction of all four factors is mandatory before hemostatic interventions can successfully increase thrombin generation.4
1. Hypothermia: A core temperature below 36°C significantly impedes coagulation cascade and platelet function.4
2. Acidosis: Systemic acidosis, defined by a pH below 7.3 or a Base Excess below -6 mmol/L, impairs clotting factor function and platelet aggregation.4
3. Coagulopathy (Acute Traumatic Coagulopathy, ATC): A complex disorder stemming from the initial injury (shock state) and compounded by hemodilution.14
4. Hypocalcemia: Ionized calcium levels below 1 mmol/L represent a critical deficiency.4 Calcium is an indispensable co-factor required for thrombin generation and is often chelated by citrate in massive transfusion. Aggressive calcium replacement, aiming for a target of Ionized Calcium (Ca2+) greater than 1.0 or 1.2 mmol/L, is thus a crucial, life-saving component of modern resuscitation.5
The prompt identification of patients requiring massive intervention is essential for improving survival.14 The Assessment of Blood Consumption (ABC) Score is a key tool utilized by professional medical organizations to rapidly predict the likelihood of a patient requiring massive transfusion (MT).16 An ABC score of 2 or more necessitates the immediate activation of a Massive Transfusion Protocol (MTP).15 The score is calculated based on four criteria, each worth one point: a penetrating injury mechanism, a systolic blood pressure (SBP) <= 90 mmHg in the emergency department (ED), a heart rate (HR) >= 120 beats per minute in the ED, and a positive Focused Assessment with Sonography in Trauma (FAST) exam.16
Non-Contrast Head Computed Tomography (CT): This is the standard neuroimaging technique, providing fast and accurate evaluation for the presence and location of ICH.
CT Angiography (CTA): Often ordered alongside the non-contrast CT to evaluate for underlying vascular pathologies, such as aneurysms or AVMs. CTA is also used to assess for the "spot sign"—a tiny, enhancing foci within the hematoma caused by contrast extravasation—which predicts a high risk of hematoma expansion.
Focused Assessment with Sonography in Trauma (FAST): Remains the primary, rapid, non-invasive, bedside imaging method for unstable trauma patients to document fluid (blood) in the abdomen, chest, and pelvis.7 CT scanning offers the highest sensitivity and specificity for diagnosing visceral and vascular injury, but ATLS guidelines strictly recommend that CT should only be performed on hemodynamically stable patients.7
Conventional laboratory tests for coagulation suffer from significant time delays, making them ineffective for guiding management during acute, ongoing hemorrhage.4 Viscoelastic Testing (TEG/ROTEM) provides a functional point-of-care alternative for real-time coagulation monitoring, with results available rapidly (typically within 10–15 minutes).4 ROTEM assays show strong correlations with conventional tests, enabling clinicians to specifically treat coagulopathic bleeding (e.g., fibrinogen deficiency or hyperfibrinolysis) rather than relying solely on generalized plasma transfusion.4 Experts advocate for the wider availability of TEG and ROTEM facilities in tertiary hospitals for all patients suffering from severe bleeding.4
Damage Control Resuscitation represents the current standard of care for trauma patients experiencing critical hemorrhage, with the ultimate institutional goal being the achievement of zero preventable deaths after injury.5 DCR is a comprehensive strategy focusing on limiting blood loss, minimizing the duration of shock, and rapidly correcting the components of the Lethal Diamond.5
The core tenets of DCR are:
1. Early Definitive Hemorrhage Control: Achieving physical or surgical control of the bleeding source.5
2. Hypotensive Resuscitation (Permissive Hypotension): Targeted blood pressure management to prevent the disruption of soft, early clots.5
3. Hemostatic Resuscitation: Early, rapid, and balanced administration of blood components (MTP activation).5
A Massive Transfusion is classically defined as the administration of 10 or more units of packed red blood cells (PRBCs) within 24 hours.15 Activation of the MTP is critical and is often triggered by criteria such as an ABC score of 2 or more or persistent hemodynamic instability.15 The core principle is the balanced transfusion ratio, typically aiming for 1:1:1 (plasma:platelets:RBCs), beginning with the first units administered, to prevent dilutional coagulopathy.6
DCR mandates stringent physiological endpoints to guide resuscitation efforts.15 The resuscitation strategy must be individualized:
● Hypotensive Targets (Non-TBI Trauma): Lower SBP targets (80–90 mmHg or MAP 60–65 mmHg) are used to limit blood loss until definitive control is achieved.15
● Higher Targets (Suspected TBI/Spinal Cord Injury): Higher pressures are mandatory for neurosurgical patients (SBP >120 mmHg or MAP >85 mmHg) to maintain adequate cerebral perfusion pressure and prevent secondary brain injury.15
Table 2: Key Clinical Targets in Damage Control Resuscitation and Massive Transfusion Protocol
Tranexamic Acid (TXA): TXA is an antifibrinolytic agent that is included in all MTP protocols.20 In trauma, TXA must be administered within a time-critical window of three hours from the time of injury to maximize its efficacy in reducing bleeding.19
Anticoagulation Reversal: Rapid reversal of pre-injury anticoagulants is mandated for all patients with serious, life-threatening hemorrhage.5 Prothrombin Complex Concentrate (PCC) is often preferred for reversing vitamin K antagonists and direct oral anticoagulants due to its efficacy and the advantage of requiring less fluid volume compared to plasma.5
Non-compressible torso hemorrhage (NCTH), particularly non-compressible abdominal hemorrhage (NCAH), represents a major cause of potentially preventable death, often requiring immediate proximal vascular control.2
Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a minimally invasive technique that provides an alternative to maximally invasive methods like resuscitative thoracotomy.21 The technique involves placing a catheter in the aorta and inflating a balloon to temporarily occlude blood flow distal to the point of injury.21 REBOA functions as a crucial temporizing measure, raising central arterial pressure and preventing exsanguination until the patient can be transported to a hybrid operating room for definitive surgical or endovascular repair.21 Evidence suggests that the odds of in-hospital mortality for patients who undergo REBOA are significantly lower compared to those managed with resuscitative thoracotomy (OR 0.18).23
Postpartum Hemorrhage (PPH) is a critical public health issue and a leading cause of maternal death worldwide.24 The World Health Organization (WHO), in collaboration with global health agencies, has issued consolidated guidelines emphasizing readiness, rapid recognition, and structured response.24 Key evidence-based interventions recommended for the management of PPH include: administration of oxytocic drugs, uterine massage, the use of Tranexamic Acid (TXA), intravenous fluids, and thorough examination of the vaginal and genital tract.24
The effective management of acute hemorrhage requires a sophisticated, systematic, and time-critical approach centered on the principles of Damage Control Resuscitation. For neurosurgical patients, the dual need for systemic stabilization (DCR) alongside specific cerebral perfusion maintenance (higher SBP targets) is paramount.5 The foundational requirement for successful hemorrhage control is the recognition and aggressive correction of the four mutually compounding physiological derangements that constitute the Lethal Diamond: hypothermia, acidosis, coagulopathy, and hypocalcemia.
Modern care emphasizes the shift from empiric volume replacement to hemostatic resuscitation, driven by Massive Transfusion Protocols (MTPs) using fixed 1:1:1 ratios of blood components. The future of hemorrhage management lies in moving beyond these fixed ratios toward truly goal-directed individualized resuscitation through the integration of real-time diagnostic tools such as TEG and ROTEM.4 Ultimately, optimizing survival hinges on rapid assessment, standardization of protocols, and seamless, multidisciplinary teamwork guided by robust, evidence-based guidelines.20
References
1. Hemorrhage- Definition, Class, Types, Disorders - Microbe Notes, accessed October 29, 2025, https://microbenotes.com/hemorrhage/
2. Management of non-compressible torso hemorrhage of the abdomen in civilian and military austere environments: a scoping review | Trauma Surgery & Acute Care Open, accessed October 29, 2025, https://tsaco.bmj.com/content/9/1/e001189
3. The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient, accessed October 29, 2025, https://www.mdpi.com/2077-0383/10/20/4793
4. Hemostatic defects in massive transfusion: an update and treatment ..., accessed October 29, 2025, https://www.researchgate.net/publication/347323594_Hemostatic_defects_in_massive_transfusion_an_update_and_treatment_recommendations
5. American Association for the Surgery of Trauma/American College ..., accessed October 29, 2025, https://pubmed.ncbi.nlm.nih.gov/37697470/
6. Adult Massive Transfusion Protocol - McGovern Medical School - UTHealth Houston, accessed October 29, 2025, https://med.uth.edu/surgery/adult-massive-transfusion-protocol/
7. Advanced Trauma Life Support®. ABCDE from a radiological point of view - PMC - NIH, accessed October 29, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC1914302/
8. Bleeding - Wikipedia, accessed October 29, 2025, https://en.wikipedia.org/wiki/Bleeding
9. Nontraumatic Intracranial Hemorrhage - Diseases of the Brain, Head and Neck, Spine 2020–2023 - NCBI, accessed October 29, 2025, https://www.ncbi.nlm.nih.gov/books/NBK554334/
10. Comparative study of traumatic and spontaneous intracerebral hemorrhage - PubMed, accessed October 29, 2025, https://pubmed.ncbi.nlm.nih.gov/11794609/
11. Intracerebral Hemorrhage - StatPearls - NCBI Bookshelf - NIH, accessed October 29, 2025, https://www.ncbi.nlm.nih.gov/books/NBK553103/
12. Major Haemorrhage in Trauma - LITFL, accessed October 29, 2025, https://litfl.com/major-haemorrhage-in-trauma/
13. Hemorrhage Classification - FPnotebook, accessed October 29, 2025, https://mobile.fpnotebook.com/ER/Exam/HmrhgClsfctn.htm
14. Pathophysiology of hemorrhagic shock - PubMed, accessed October 29, 2025, https://pubmed.ncbi.nlm.nih.gov/35044060/
15. Massive Transfusion - StatPearls - NCBI Bookshelf, accessed October 29, 2025, https://www.ncbi.nlm.nih.gov/books/NBK499929/
16. ABC Score for Massive Transfusion - MDCalc, accessed October 29, 2025, https://www.mdcalc.com/calc/1228/abc-score-massive-transfusion
17. acs tqip - best practices guidelines in imaging - Washington State Department of Health, accessed October 29, 2025, https://doh.wa.gov/sites/default/files/legacy/Documents/2900//ImagingGuidelines.pdf
18. Damage control resuscitation - :: Clinical and Experimental Emergency Medicine, accessed October 29, 2025, https://www.ceemjournal.org/upload/pdf/ceem-19-089.pdf
19. Massive Transfusion for Trauma - Washington State Department of Health, accessed October 29, 2025, https://www.doh.wa.gov/Portals/1/Documents/Pubs/530180.pdf
20. Toward Standardized Massive Transfusion Protocols: A Multicenter Evaluation of Practice Variability Within a National Trauma System, accessed October 29, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12346504/
21. (PDF) Use of Damage Control Surgery and Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Penetrating Torso Trauma: A Systematic Review - ResearchGate, accessed October 29, 2025, https://www.researchgate.net/publication/395435646_Use_of_Damage_Control_Surgery_and_Resuscitative_Endovascular_Balloon_Occlusion_of_the_Aorta_REBOA_in_Penetrating_Torso_Trauma_A_Systematic_Review
22. Management of non-compressible torso hemorrhage: An update - PMC - PubMed Central, accessed October 29, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8173581/
23. A comparison of mortality and indicators of treatment success of resuscitative endovascular balloon occlusion of aorta (REBOA): a systematic review and meta-analysis - PMC - NIH, accessed October 29, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9794671/
24. Global health agencies issue new recommendations to help end deaths from postpartum haemorrhage, accessed October 29, 2025, https://www.who.int/news/item/05-10-2025-global-health-agencies-issue-new-recommendations-to-help-end-deaths-from-postpartum-haemorrhage
25. Consolidated guidelines for the prevention, diagnosis and treatment ..., accessed October 29, 2025, https://www.who.int/publications/i/item/9789240115637
26. Trauma Care Principles - StatPearls - NCBI Bookshelf, accessed October 29, 2025, https://www.ncbi.nlm.nih.gov/books/NBK547757/
