Variceal Haemorrhage

Meet the patient

A 56-year-old man with known alcoholic cirrhosis is brought to the emergency department after vomiting a bowl of fresh red blood. He is drowsy, heart rate 124, blood pressure 84/52, with spider naevi, ascites, and a palpable spleen. His wife says he was well yesterday until a fever and abdominal pain began overnight.[1]

This is an acute variceal bleed, and the next two hours run on four parallel tracks that never wait for each other: secure the airway and the circulation, start the vasoactive drug and the antibiotic before the scope, get to endoscopy within 12 hours, and decide early whether this is a pre-emptive-TIPS patient. The fever overnight is the clue — infection precipitates bleeding, and the antibiotic is not optional.[1][3]

Three numbers that own the topic — 5, 12, 20

The hepatic venous pressure gradient (HVPG) is the single measure that frames the whole disease, and three thresholds govern it. Reproduce them in one breath.[1]

• HVPG over 5 mmHg — portal hypertension is present (normal is 3 to 5).
• HVPG over 10 mmHg — clinically significant portal hypertension; varices and ascites begin to appear.
• HVPG over 12 mmHg — the bleeding threshold; varices are at risk of rupture.[1]

The number rule: 5, 12, 20. Five defines portal hypertension, twelve is the bleeding threshold, twenty percent is the haemodynamic response to a beta-blocker. Reducing the HVPG to below 12 mmHg, or by at least 20 percent from baseline, virtually abolishes the risk of bleeding — and that is the goal of pharmacological prevention.[1]

[1]

Why varices form and bleed — Laplace, not luck

Portal hypertension is a balance between resistance to flow and the inflow of blood, and cirrhosis breaks both arms. Resistance rises through fixed fibrosis and nodules (structural) and through the contraction of activated hepatic stellate cells driven by endothelin-1, angiotensin II, and sympathetic signalling against deficient intrahepatic nitric oxide (dynamic, and reversible — the rationale for terlipressin). Inflow rises because excess splanchnic nitric oxide and glucagon dilate the splanchnic bed, completing a vicious circle: high resistance raises pressure, vasodilation raises inflow, pressure climbs higher still.[1]

Sustained pressure reopens the embryonic portosystemic channels at the gastro-oesophageal junction. The left gastric (coronary) vein and the short gastric veins drain into the azygos and systemic circulation through the submucosa of the distal oesophagus and gastric fundus. As flow rises, these thin-walled submucosal veins dilate, elongate, and become tortuous — varices — sitting just beneath a thin mucosa in a region of high pressure.[1]

Rupture is a mechanical failure governed by wall tension — Laplace's law.[1]

Wall tension = (transmural pressure x varix radius) divided by wall thickness.[1]

As a varix enlarges (radius rises) and its wall thins (thickness falls) while pressure stays high, wall tension climbs steeply until it exceeds the tensile strength of the wall — empirically at an HVPG above 12 mmHg. This is why a large varix with red wale signs bleeds, and why lowering the pressure is the whole of prevention.[1]

Oesophageal varices bleed more often; gastric varices bleed more torrentially. Oesophageal varices arise in the distal 5 cm of the oesophagus (supplied by the left gastric vein) and are the commonest and most likely to bleed. Gastric varices lie in the fundus (supplied by the short gastric veins), bleed less often, but bleed far more torrentially when they do — which is why they need cyanoacrylate glue, not band ligation.[7]

The four-step bundle — run the tracks in parallel

The first hour decides survival, and the four tracks run concurrently — not sequentially. Resuscitation does not wait for endoscopy, and endoscopy does not wait for a normal INR.[1][2]

[1]

Track 1 — resuscitation, and the restrictive transfusion

Airway first, always. Intubate early if there is ongoing massive haematemesis, active grade 3 to 4 encephalopathy, agitation precluding safe endoscopy, or hypoxaemia from aspiration. A protected airway is also the prerequisite for unhurried endoscopic therapy — aspiration of blood is a leading cause of death.[1]

Circulation: two large-bore 14 G or 16 G cannulae, group and crossmatch 4 to 6 units, balanced crystalloid. Then apply the restrictive transfusion strategy — the first of two interventions proven to reduce mortality.[1]

The Villanueva trial (NEJM 2013) settled the counter-intuitive rule that less transfusion saves more lives. Patients with acute upper GI bleeding were randomised to a restrictive strategy (transfuse at a haemoglobin of 70 g/L, target 70 to 80) versus a liberal strategy (transfuse at 90, target 90 to 100). The restrictive group had better survival, less rebleeding, and fewer complications — because over-transfusion raises central and portal venous pressure, dislodging clots and worsening bleeding, and because stored blood carries dysfunctional platelets and clotting factors.[2]

Transfuse more generously only in defined exceptions: massive exsanguinating bleeding (resuscitate to perfusion, not a number), coronary artery disease or unstable angina (the trial excluded these — target around 80 to 90), and shock at presentation (restore perfusion first, then ease to the restrictive target).[1]

Coagulopathy correction is judicious, not automatic. The cirrhotic coagulopathy is a rebalanced haemostasis — procoagulant and anticoagulant factors fall together — so an isolated raised INR does not by itself predict bleeding. Give vitamin K 10 mg IV slowly (correcting vitamin-K-dependent factor deficiency from cholestasis or antibiotics); reserve fresh frozen plasma and platelets for active bleeding with an INR over 1.5 or platelets under 50, since over-correction risks volume overload and worsened portal pressure. Tranexamic acid is not recommended — the HALT-IT trial showed no mortality benefit and possible harm.[1]

Track 2 — vasoactive drug plus antibiotic, before the scope

Two drugs start before endoscopy, and both are mortality-reducing. They are the recurring omissions that cost marks and lives.[1]

The vasoactive drug causes splanchnic vasoconstriction, lowering portal inflow and buying time for endoscopy. Give before endoscopy and continue for 2 to 5 days.[1]

• Terlipressin — 2 mg IV bolus, then 1 mg every 4 hours for 48 hours, then 1 mg every 4 hours (reduced to 0.5 mg if tolerated) up to 5 days. The agent of choice in the UK and India. Caution: hyponatraemia and ischaemia (coronary, mesenteric, peripheral); avoid in pregnancy unless essential.
• Octreotide — 50 microgram IV bolus, then 50 microgram per hour infusion for 3 to 5 days. Common in North America; less potent than terlipressin but better tolerated.
• Somatostatin — 250 microgram bolus then 250 microgram per hour; an alternative where available.[1]

Prophylactic antibiotic is the second mortality-reducing intervention, and it goes to every cirrhotic with a bleed. Infection both precipitates and complicates variceal bleeding, and prophylactic antibiotics reduce infection, rebleeding, and death.[3]

• Ceftriaxone 1 g IV once daily for up to 7 days — the preferred agent, superior to oral norfloxacin or ciprofloxacin in trials, particularly in high-resistance regions.
• Oral norfloxacin 400 mg twice daily or ciprofloxacin — alternatives in low-resistance settings or as a step-down.[1]

[1] [3]

Track 3 — endoscopy within 12 hours, band versus glue

Endoscopy is both diagnostic and therapeutic, and it is the single most important investigation. It is performed within 12 hours of admission, after resuscitation and the start of the vasoactive drug and antibiotic — and not delayed to normalise the coagulation.[1]

• Oesophageal varices — endoscopic band ligation (EBL). A rubber band is suction-applied onto each varix, ligating and strangulating it. First-line therapy; achieves haemostasis in 80 to 90 percent. Repeat sessions every 2 to 4 weeks until obliteration, then surveillance.
• Gastric varices — cyanoacrylate (glue) injection. A tissue adhesive (N-butyl-2-cyanoacrylate, often mixed with lipiodol) polymerises and occludes the varix. First-line for gastric, especially fundal, varices, where band ligation is less effective and more prone to rebleed. Risks: glue embolisation (pulmonary, cerebral, splenic).
• Sclerotherapy — largely superseded by EBL (more complications: ulceration, strictures, sepsis); reserved for bleeding that cannot be banded.[1]

Combination therapy — a vasoactive drug plus endoscopic band ligation — is superior to either alone at controlling acute bleeding and reducing 5-day mortality. Both should be in place by 12 hours.[1]

Endoscopy also assigns the cause, because a known varix does not exclude another source. Up to a third of upper GI bleeds in cirrhosis are non-variceal — peptic ulcer, Mallory-Weiss tear, gastritis, malignancy, Dieulafoy, aortoenteric fistula. In a cirrhotic with haematemesis, assume variceal until endoscopy proves otherwise, but be ready for a non-variceal cause.[2]

Track 4 — balloon tamponade as a bridge, then rescue or pre-emptive TIPS

When endoscopic control fails, the bridge is temporary and the destination is TIPS. A Sengstaken-Blakemore tube (gastric and oesophageal balloons) or a Linton or Minnesota tube (gastric balloon only) is inserted and the gastric balloon inflated against the gastro-oesophageal junction to tamponade the bleeding. It is used only when endoscopic control fails, as a bridge of no more than 24 hours to definitive TIPS. Risks — aspiration, oesophageal ulceration and rupture, airway obstruction — mean the patient must be intubated and in an ICU. A self-expanding metal oesophageal stent is a safer alternative bridge where available.[1]

TIPS — the transjugular intrahepatic portosystemic shunt — is the rescue therapy and the pre-emptive therapy. It creates a stented channel between the hepatic vein and the intrahepatic portal vein, decompressing the portal system.[1]

• Rescue TIPS — for failure to control bleeding despite drugs plus endoscopy.
• Pre-emptive (early) TIPS within 72 hours in high-risk patients, defined by Baveno: Child-Pugh C, score 7 to 13, OR Child-Pugh B with active bleeding at endoscopy. Pre-emptive TIPS reduces both rebleeding and mortality (Monescillo 2004; Garcia-Pagan 2010). Do not apply it to Child-Pugh over 13, or to patients with uncontrolled sepsis, severe cardiopulmonary disease, or extensive portal vein thrombosis.[5]

TIPS complications to name: hepatic encephalopathy in up to a third (the shunted blood bypasses hepatic detoxification), heart failure from increased venous return, haemolysis, and shunt dysfunction (stenosis or thrombosis).[1]

Prevention — primary and secondary, both aimed at the pressure

Without secondary prevention, rebleed risk is 60 to 70 percent within a year — so every acute-bleed survivor moves straight into the prevention ladder. Both ladders aim at the same target: lower the HVPG below 12 or by at least 20 percent.[1]

Primary prevention (the patient who has varices but has never bled) — indicated for medium or large varices, or small varices with red wale signs or Child-Pugh B or C:[1]

• Option A — non-selective beta-blocker. Propranolol 20 to 40 mg orally twice daily, nadolol 40 to 80 mg orally daily, or carvedilol 6.25 to 12.5 mg orally daily, titrated to a resting heart rate of 55 to 60. Carvedilol is now preferred because its alpha-1 blockade lowers portal pressure more than propranolol (Tripathi 2009).
• Option B — endoscopic band ligation — for those intolerant of an NSBB or with contraindications (asthma, heart block, hypotension). Serial sessions until obliteration, then surveillance.
• NSBB and EBL are broadly equivalent for first-bleed prevention; combine only in selected high-risk cases.[6]

Secondary prevention (the patient who has survived a variceal bleed):[1]

• Combination therapy — NSBB plus serial band ligation — gives the lowest rebleed rate and is first-line.
• TIPS if rebleeding despite combination therapy, or intolerance of an NSBB.
• Liver transplantation for decompensated cirrhosis — refer early, MELD-driven.[8]

The scores that drive the TIPS and transplant decisions

Child-Pugh and MELD-Na are reproduced verbatim because they decide pre-emptive TIPS and transplant listing.[1]

Child-Pugh — five components, each 1 to 3 points:[1]

[1]

Classes: A is 5 to 6 (well-compensated); B is 7 to 9 (significant functional compromise); C is 10 to 15 (decompensated). Child-Pugh C, especially 7 to 13, carries the highest peri-bleed mortality and is a pre-emptive TIPS criterion.[5]

MELD-Na predicts 90-day mortality and drives transplant listing. A MELD over 18 in a bleeding cirrhotic predicts poor outcome and warrants transplant referral. The Baveno VII non-invasive rule: a liver stiffness over 25 kPa rules in clinically significant portal hypertension; platelets over 150,000 with stiffness under 25 rule out high-risk varices and can safely avoid screening endoscopy.[1]

How variceal-bleed patients come to harm — the preventable list

• Over-transfusing to a normal haemoglobin — raises portal pressure and worsens rebleeding (Villanueva).[2]
• Forgetting the prophylactic antibiotic — the commonest omission and the easiest mortality win.[3]
• Delaying endoscopy to normalise the INR — the cirrhotic INR is rebalanced haemostasis, not a bleeding predictor; endoscopy is therapeutic and must not wait.[1]
• Leaving a balloon tamponade in beyond 24 hours — oesophageal necrosis and rupture.[1]
• Not offering pre-emptive TIPS to a Child-Pugh C patient with active bleeding — a clear mortality-reducing intervention missed.[5]
• Not starting secondary prevention after the acute episode — the next, often fatal, bleed.[1]
• An unprotected airway during massive haematemesis — aspiration pneumonia, a leading cause of death.[1]

The trials that built the bundle

[2] [3] [5] [6]

Monescillo 2004 (Hepatology) showed that early TIPS in high-risk patients reduced treatment failure and mortality — the precursor to the Garcia-Pagan 2010 trial.[4] Sarin 1992 established the gastric varices classification (GOV1, GOV2, IGV1, IGV2) still in use.[7] The AASLD 2007 guidance (Garcia-Tsao) set the comprehensive prevention and management framework.[8]

Special populations — what changes

Pregnancy. Variceal bleed risk is highest in the second trimester, when the gravid uterus compresses the IVC and increases splanchnic venous pressure. Screen and treat known varices before conception where possible. In an acute bleed, endoscopic band ligation is first-line and safe in pregnancy; use terlipressin with caution (uterine vasoconstriction and ischaemia — octreotide preferred by some); balloon tamponade and TIPS are last resorts, TIPS only after the second trimester. Vaginal delivery is generally advised with a covered second stage; caesarean for obstetric indications.[1]

Children. The leading cause of variceal bleeding in children is extrahepatic portal vein obstruction (cavernous transformation), with preserved liver synthetic function. Manage with endoscopic band ligation or sclerotherapy; a surgical portosystemic shunt (meso-Rex bypass) for refractory cases also restores portal flow to the liver.[1]

The elderly. Higher per-bleed mortality, atypical presentation (confusion, falls, painless melaena), more comorbidity, more anticoagulant and antiplatelet use. Lower threshold to intubate for airway protection. Stop NSAIDs.[1]

The anticoagulated or antiplatelet patient. Hold the agent; reverse only if bleeding is life-threatening (prothrombin complex concentrate for warfarin, specific reversal agents for DOACs where available). Resume anticoagulation as soon as haemostasis is secure — the thrombotic risk off-treatment is substantial.[1]

The patient with HCC. Portal vein tumour thrombus worsens portal hypertension and complicates TIPS; treat the HCC alongside the varices.[1]

The mantra

The mantra: restrict the transfusion, give the antibiotic to every cirrhotic, start the vasoactive before the scope, band within twelve hours — and put a TIPS in the Child-Pugh C patient early.[1][2][3]

Ward-round test — three stems, thirty seconds each

Stem 1 — the man from the top of the topic (answer)

The 56-year-old cirrhotic who vomited a bowl of blood, heart rate 124, blood pressure 84/52, drowsy, with overnight fever and abdominal pain. What do you start before the endoscopy? Model: This is an acute variceal bleed — start the bundle before the scope. Protect the airway (intubate early if encephalopathic or uncontrolled), two large-bore cannulae, group and crossmatch 4 to 6 units, and a restrictive transfusion to a haemoglobin of 70 to 80. Start terlipressin 2 mg IV then 1 mg every 4 hours and ceftriaxone 1 g IV daily — both before endoscopy — because the overnight fever flags infection as a precipitant and the antibiotic reduces mortality. Book endoscopy within 12 hours for band ligation. Do not delay the scope to normalise the INR. Plan pre-emptive TIPS within 72 hours if he is Child-Pugh C 7 to 13 or Child-Pugh B with active bleeding at endoscopy.[1][3]

Stem 2 — the well-meaning registrar transfusing to Hb 100 (answer)

A registrar transfuses a bleeding cirrhotic to a haemoglobin of 100 g/L to be safe. Why is that the wrong instinct, and what is the target? Model: Over-transfusion raises central and portal venous pressure, dislodging clots and worsening rebleeding, and stored blood carries dysfunctional platelets and clotting factors. The Villanueva 2013 trial showed that a restrictive strategy — transfusing at a haemoglobin of 70 g/L, target 70 to 80 — improved survival and reduced rebleeding versus a liberal target of 90. The target is 70 to 80 g/L, with higher thresholds only for massive exsanguinating bleeding, coronary artery disease, or shock at presentation. The instinct to transfuse to normal is exactly the error the trial was designed to correct.[2]

Stem 3 — the Child-Pugh C patient with active bleeding (answer)

A bleeding cirrhotic is Child-Pugh C, score 11, with active spurting at endoscopy despite band ligation and terlipressin. What is the next decision? Model: This is a pre-emptive TIPS candidate — Child-Pugh C 7 to 13 with active bleeding meets the Baveno VII high-risk criteria, and TIPS within 72 hours reduces both rebleeding and mortality (Garcia-Pagan 2010). If bleeding is uncontrolled right now, use a balloon tamponade or a covered self-expanding metal stent as a bridge of no more than 24 hours, intubated and in ICU, then proceed to rescue TIPS. Do not apply pre-emptive TIPS to Child-Pugh over 13 or to uncontrolled sepsis or severe cardiopulmonary disease. After control, start secondary prevention with an NSBB plus serial band ligation, and refer for transplant.[5]

References

1. [1]de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension J Hepatol, 2022.PMID 35120736
2. [2]Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding N Engl J Med, 2013.PMID 23281973
3. [3]Bernard B, Grangé JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis Hepatology, 1999.PMID 10347104
4. [4]Monescillo A, Martínez-Lagares F, Ruiz-del-Arbol L, et al. Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding Hepatology, 2004.PMID 15382120
5. [5]García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding N Engl J Med, 2010.PMID 20573925
6. [6]Tripathi D, Ferguson JW, Kochar N, et al. Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed Hepatology, 2009.PMID 19610055
7. [7]Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients Hepatology, 1992.PMID 1446890
8. [8]Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis Hepatology, 2007.PMID 17879356