Bleeding per Rectum: Aetiology, Diagnosis & Approach to Management

Bleeding per rectum: An overview

Rectal bleeding, which means bleeding from a site distal to ligament of Treitz, is a manifestation of lower gastrointestinal bleed.¹Zia N, Hussain T, Salamat A, et al. J Ayub Med Coll Abbottabad 2008;20(1).   Lower gastrointestinal (GI) bleeding is a frequent cause of hospital admission and is a factor in hospital morbidity and mortality. Lower GI bleeding can be mild and intermittent, as often is the case of angiodysplasia and colon carcinoma, or moderate or severe, as may be the situation in diverticula-related bleeding. However, colon carcinoma rarely causes significant lower GI bleeding.²Available at: http://emedicine.medscape.com/article/188478-overview. Accessed on: Feburary 28, 2015.  

Pathophysiology of lower GI bleeding

Rectal bleeding is usually suspected when patients complain of haematochezia, and it may be overt, occult or obscure. Overt bleeding can be acute, massive or chronic. Acute lower GI bleeding is characterised as melena (the passage of black, tarry, foul-smelling stools as a result of degradation of blood to hematin) or haematochezia (passage of maroon or bright red blood or blood clots per rectum, with or without stool). Occult bleeding is bleeding not apparent to the patient and is usually detected with stool guaiac testing. It is the most common presentation of lower GI bleeding in the elderly, occurring in 10% of the adult population. Remarkably, patients can loose up to 100 mL of blood per day and still have grossly normal appearing stools. Obscure bleeding is bleeding in which the source of bleeding is difficult to detect on routine endoscopic and radiologic examinations and it is unidentified in approximately 5 % of patients who present with GI bleeding.⁴Chait MM. World J Gastrointest Endosc. May 16, 2010; 2(5): 147-154.  

Causes of rectal/lower GI bleeding

Rectal/lower GI bleeding may be grouped into several categories: anatomic (diverticulosis); vascular (angiodysplasia, ischaemic); inflammatory (infectious, idiopathic, radiation-induced) and neoplastic.

Box 1 lists the most common causes of colonic/rectal bleeding. The incidence of underlying causes of lower GI bleeding varies

between age groups. For example, younger patients under 30 years are more likely to have haemorrhoids, anal fissure or inflammatory bowel disease whereas a patient over the age of 50 years with rectal bleeding has a higher risk of colorectal cancer.³Commissioning guide 2013. Rectal Bleeding. Available at: www.nice.org.uk/accreditation  

Prevalence of rectal bleeding

The incidence of lower GI bleeding increases with age and is more common in men than women. There are many gastrointestinal diseases that cause lower GI bleeding in the elderly. Worldwide regional differences have been seen in the causes of lower GI bleeding. In the countries of Western Europe and the United States the most common causes of lower GI bleeding are diverticular disease and vascular ectasias. Less common causes of lower GI bleeding are inflammatory diseases of the colon, neoplasms, postpolypectomy haemorrhage, haemorrhoids, stercoral ulcer and solitary rectal ulcer. Rare causes include Dieulafoy’s lesion and colorectal varices. However, in Asia, the most common causes of lower GI bleeding are haemorrhoids, anal fissures and malignant colorectal neoplasms. Less common causes are benign colorectal neoplasms, ulcerative colitis, infectious colitis, ischaemic colitis and radiation colitis. Diverticulosis coli is remarkably a rare cause of lower GI bleeding in Asia.⁴Chait MM. World J Gastrointest Endosc. May 16, 2010; 2(5): 147-154.  

Factors affecting the severity of bleeding per rectum in elderly

Co-morbid disease and polypharmacy are the two main factors that directly affect morbidity and mortality in elderly patients with lower GI bleeding. Co-morbid diseases, such as cardiovascular disease, diabetes mellitus and malignancy, have a significant impact on the incidence and severity of lower GI bleeding, while polypharmacy with the use of NSAIDS and anticoagulants increases bleeding in such patients.⁴Chait MM. World J Gastrointest Endosc. May 16, 2010; 2(5): 147-154.  

Diagnostic evaluation/assessment/management of rectal bleeding

Primary assessment (according to NICE guidelines)³Commissioning guide 2013. Rectal Bleeding. Available at: www.nice.org.uk/accreditation  

• Careful attention to history, presence or absence of perianal symptoms, age of patient (in view of likely differential diagnosis with each age group), family history of colorectal malignancy and red flag symptoms including weight loss, symptoms suggestive of anaemia and change in bowel habit.
• Examination of the abdomen to exclude abdominal mass and digital rectal examination (DRE) to examine for fissure and exclude rectal cancer may be useful.
• Baseline blood tests may be useful in selected cases, e.g. full blood count (FBC). Other blood tests will only be necessary if there are other features in the history, e.g. unexplained weight loss.
• Faecal calprotectin is a useful screening tool in younger, lower risk patient with suspected inflammatory bowel disease. A positive faecal calprotectin result has a high positive predictive value (PPV) for finding inflammatory bowel disease at colonoscopy. It also costs less as compared to flexible sigmoidoscopy.
• Proctoscopy is useful for primary care clinicians as a screening tool in patients with rectal bleeding, however it should not be used as a substitute for flexible sigmoidoscopy to rule out serious pathology.

Primary care management (as per NICE guidelines)

• In low risk patients with rectal bleeding, their symptoms should be managed with treatment and ‘watch and wait’ policy should be adopted.
• Patients with symptomatic haemorrhoids should be given topical treatment, oral fluid intake, high fibre diet and fibre supplementation.
• Patients with acute anal fissure may be treated with dietary advice and a bulking agent.
• Topical glyceryl trinitrate (GTN) 0.4% ointment should be considered for chronic fissures (duration of symptoms > 6 weeks or clinical appearances of chronicity).

Secondary assessment (determination of source of bleeding)

As per NICE guidelines, in acute colonic haemorrhage,

• Localisation of the site and determination of the cause of bleeding allows treatment to be appropriately focused. Localisation techniques utilise endoscopic, radiological and nuclear scintigraphic modalities.
• The cause and site of massive lower gastrointestinal haemorrhage should be determined following the early use of colonoscopy and use of computed tomography scanning, computed tomography angiography or digital subtraction angiography.
• Nuclear scintigraphy should be considered to assist in localisation of bleeding in patients with significant recent haemorrhage.

Referral criteria (as per NICE guidelines)

Any of the following patient with rectal bleeding, should be referred urgently under the two week wait guidelines as recommended by NICE Referral Guidelines for Suspected Cancer:

• aged ≥ 40 years with rectal bleeding and change in bowel habit towards looser and/or more frequent stools for 6 weeks or more.
• aged ≥ 60 years with rectal bleeding persisting for 6 weeks or more without change in bowel habit and without anal symptoms.
• rectal bleeding and a palpable rectal mass.

Investigation following referral

• Flexible sigmoidoscopy is the investigation of choice for patients < 45 yrs with persistent rectal bleeding, who have received treatment for haemorrhoids and still have persistent bleeding.
• If there is a family history of colorectal malignancy, colonoscopy may be a better investigation for rectal bleeding as these patients have a higher risk of right colon cancers. British Society of Gastroenterology guidelines recommend one-off colonoscopy at 55 years or over in asymptomatic individuals with one first-degree relative diagnosed with colorectal cancer under 50 years old, or two (or more) first degree relatives diagnosed at any age.
• Patients > 45 yrs with persistent rectal bleeding should be offered either colonoscopy or flexible sigmoidoscopy. In elderly, frail or unfit patients, CT colonography with flexible sigmoidoscopy may be better tolerated than colonoscopy.

Secondary care of patients with rectal bleeding

Anal fissures

NICE guidelines say, if a patient with a chronic anal fissure has previously used GTN ointment, the first line options in secondary care are topical diltiazem 2% or injection of botulinum toxin. Surgical options for anal fissure include fissurectomy with injection of botulinum toxin and lateral internal anal sphincterotomy.³Commissioning guide 2013. Rectal Bleeding. Available at: www.nice.org.uk/accreditation  

Haemorrhoids

According to NICE, rubber band ligation is currently the best available outpatient treatment for haemorrhoids. About 20% of patients require a second banding procedure within six months for symptom control. At present surgery is reserved for bleeding or prolapsing haemorrhoids that have not responded to outpatient treatment. Doppler-guided haemorrhoidal artery ligation and stapled haemorrhoidopexy are alternatives to formal haemorrhoidectomy. These are associated with lower pain scores.³Commissioning guide 2013. Rectal Bleeding. Available at: www.nice.org.uk/accreditation  

Management of patients admitted with severe colonic haemorrhage⁵No authors listed. Management of acute upper and lower gastrointestinal bleeding. A national clinical guideline. NHS,Sept2008. Scottish Intercollegiate .Guidelines Network  

• These patients should receive resuscitation and transfusion, if required, to restore circulatory volume. Colonic imaging is an appropriate investigation to exclude neoplasia and determine an underlying cause.
• In such patients, colonoscopic haemostasis is an effective means of controlling haemorrhage from active diverticular bleeding or post-polypectomy bleeding, when appropriately skilled expertise is available.
• If colonoscopy fails to define site of bleeding and control haemorrhage, angiographic transarterial embolisation is recommended as an effective means of controlling haemorrhage.
• Localised segmental intestinal resection or subtotal colectomy is recommended for the management of colonic haemorrhage uncontrolled by other techniques.

Role of diosmin in the treatment of haemorrhoids

Diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources or derived from the flavonoid hesperidin. Diosmin (C28H32O15)⁷Available at: https://pubchem.ncbi.nlm.nih.gov/compound/5281613#section=Top. Accessed on: Feburary 28, 2015.   differs molecularly from hesperidin by the presence of a double bond between two carbon atoms in diosmin’s central carbon ring.⁸Available at: https://pubchem.ncbi.nlm.nih.gov/compound/10621#section=Top. Accessed on: Feburary 28, 2015.  

Pharmacokinetic investigations have shown diosmin is rapidly transformed by intestinal flora to its aglycone form, diosmetin. Diosmetin is absorbed and rapidly distributed throughout the body with a plasma half-life of 26-43 hours. Diosmetin is degraded to phenolic acids or their glycine-conjugated derivatives and eliminated through the urine. Diosmin or diosmetin not absorbed is eliminated in the faeces.⁹ Diosmin. Monograph Altern Med Rev. 2004 Sep;9(3):308-11.  

Diosmin reduces inflammation and increases vein tonicity, two important factors that contribute to haemorrhoids. Diosmin is also suggested to significantly shorten the duration of haemorrhoid bleeding as well as reduce the postoperative pain significantly.¹⁰Ba-bai-ke-re MM, Huang HG, Re WN, et al. World J Gastroenterol. 2011 Mar 21;17(11):1448-56.  

Several large clinical trials have demonstrated diosmin to be effective in the treatment of acute and chronic symptoms of haemorrhoids. Results of an open field study performed in France, in which about 1000 physicians and 6759 patients took part also confirmed the effectiveness of diosmin, in the treatment of venous insufficiency (89-97%) and haemorrhoids (94-97%).¹¹Gobet A. Med. Prat. 1978, (1-2), 713-714   Availability of its micronised form, which increases its bioavailability, has led to further improvement in its efficacy (Figure 1).¹²Garner RC, Garner JV, Gregory S, et al. J Pharm Sci. 2002 Jan;91(1):32-40  ¹³Shoab SS, Porter JB, Scurr JH, et al. J Vasc Surg, 2000;31:456-61.  Moreover, standardised, purified and micronised diosmin is without any impurities as compared to hesperidin, which is associated with

unwanted side effects. Thus purified and micronised disomin can be beneficial in reducing the grade of haemorrhoids and consequently the urgency and even the necessity for surgical interventions. One randomised double-blinded, placebocontrolled study by Jiang and colleagues reported 7-day micronised purified diosmin vs placebo treatment to safely and significantly alleviate pain, oedema and bleeding in patients with acute haemorrhoidal disease.¹⁴Jiang ZM, Cao JD. Curr Med Res Opin. 2006 Jun;22(6):1141-7.  

A study by Dimitroulopoulos and team observed that when patients with grades I and II acute internal haemorrhoids were treated with oral micronised diosmin along with infrared photocoagulation, after 5 days of treatment, 74.8% of patients had no bleeding symptoms as compared to individual treatments.¹⁵Dimitroulopoulos D , Tsamakidis K, Xinopoulos D, et al. Clin Ther. 2005 Jun;27(6):74654.   In other study by Misra and Parshad, 100 outpatients with acute bleeding from internal haemorrhoids were randomised to receive micronised purified diosmin (n=50) & placebo (n=50) for 90 days. On the third day of treatment, acute bleeding was ceased in 40 (80%) patients taking diosmin as compared to 19 (38%) receiving placebo.¹⁶Misra MC , Parshad R. Br J Surg. 2000 Jul;87(7):86872.  

Evidence in haemorrhoids of grade I-IV

The use of purified diosmin was investigated in a group of 66 patients suffering from haemorrhoids of grade 1-4. Diosmin was given at a dose of 900mg twice daily for the first 7 days, then at 450mg twice daily for up to 2 months. The results confirmed diosmin efficacy in decreasing both pain and bleeding (Figure 2) in these patients. Diosmin also proved to have excellent tolerability.¹⁷Diana G, Catanzaro M, Ferrara A, Ferrari P. Clin Ter. 2000 Sep-Oct;151(5):341-4.  

Evidence in internal haemorrhoids of pregnancy

A study by Buckshee and team assessed the safety, efficacy and acceptability of a micronised flavonoid formulation (micronised diosmin 90% and hesperidin 10%) in the treatment of internal haemorrhoids of pregnancy.¹⁸Buckshee K, Takkar D, Aggarwal N. Int J Gynaecol Obstet. 1997 May;57(2):145-51.  

This was an open study on hospital outpatients in 50 women with acute haemorrhoids, where the treatment was given for a median of 8 weeks before delivery and 4 weeks after delivery. The outcome measures were symptoms and signs of haemorrhoids, adverse effects and acceptability of treatment.

It was observed that, by the 4th day, 66% had relief from acute symptoms of haemorrhoids and 53.6% fewer patients had relapse in the antenatal period. Treatment was well accepted and did not affect pregnancy, foetal development, birth weight, infant growth and feeding.

Evidence in the management of bleeding in nonprolapsed haemorrhoids

In a Chinese study by Ho et al.,¹⁹Ho YH, Tan M, Seow-Choen F. Dis Colon Rectum. 2000 Jan;43(1):66-9.   162 patients were randomly assigned into 3 groups: group 1 (Patients receiving only ispaghula husk), Group 2 (patients receiving rubber band ligation plus ispaghula husk, Group 3 (patients receiving micronised purified diosmin plus ispaghula husk). Haemorrhoidal bleeding was relieved most expediently in the Group 3 (Figure 3). No complications or side-effects were reported in patients receiving micronised diosmin.

Evidence in the management of pre and posthaemorrhoidectomy symptoms

An observer blinded, randomised, placebo controlled trial was conducted to compare post-haemorrhoidectomy symptoms with use of purified micronised diosmin.

Eighty-six consecutive patients with grades III and IV acute mixed haemorrhoids who were admitted in the hospital were included in the study and were randomly allocated to receive micronised diosmin 500 mg for 1 wk (n = 43) or placebo (n = 43). Post Milligan- Morgan open haemorrhoidectomy, treatment was started on the 6th day after surgery.

There was a statistically significant improvement in heaviness, bleeding, pruritus from baseline to the 8th week after operation (p < 0.05) (Table 1). Patients taking diosmin had a shorter hospitalisation stay after surgery (p = 0.03), experienced significantly less pain at 6 and 12 h after surgery (Figure 4) and less defecation pain as compared to placebo group.¹⁰Ba-bai-ke-re MM, Huang HG, Re WN, et al. World J Gastroenterol. 2011 Mar 21;17(11):1448-56.  

Purified Diosmin also helps the patient prepare for surgery as it relieves inflammation, discharge & edema and thus demarcates the area of operation. Moreover purified Diosmin may be used in conjunction with sclerotherapy, surgery & compression therapy.¹⁷Diana G, Catanzaro M, Ferrara A, Ferrari P. Clin Ter. 2000 Sep-Oct;151(5):341-4.  

Conclusion

Lower GI haemorrhage/rectal bleeding is defined as bleeding that originates from a source distal to the ligament of Trietz. It is a frequent cause of hospital admission and is a factor in hospital morbidity and mortality. The incidence of underlying causes of lower GI bleeding varies between age groups, but the most common causes include diverticular disease, vascular malformations (angiodysplasia), ischaemic colitis, haemorrhoids, inflammatory bowel disease (e.g., ulcerative proctitis, Crohn’s disease), neoplasia (carcinoma or polyps) and radiation enteropathy. Localisation of the site and determination of the cause of bleeding in acute colonic haemorrhage allows treatment to be appropriately focused. Several large clinical trials have demonstrated diosmin to be effective in the treatment of acute and chronic symptoms of haemorrhoids.

References

1. 1. Zia N, Hussain T, Salamat A, et al. J Ayub Med Coll Abbottabad 2008;20(1).
2. 2. Available at: http://emedicine.medscape.com/article/188478-overview. Accessed on: Feburary 28, 2015.
3. 3. Commissioning guide 2013. Rectal Bleeding. Available at: www.nice.org.uk/accreditation
4. 4. Chait MM. World J Gastrointest Endosc. May 16, 2010; 2(5): 147-154.
5. 5. No authors listed. Management of acute upper and lower gastrointestinal bleeding. A national clinical guideline. NHS,Sept2008. Scottish Intercollegiate .Guidelines Network
6. 6. Zuccaro G. AJG – August 1998; 93(8):1202-1208.
7. 7. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/5281613#section=Top. Accessed on: Feburary 28, 2015.
8. 8. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/10621#section=Top. Accessed on: Feburary 28, 2015.
9. 9. Diosmin. Monograph Altern Med Rev. 2004 Sep;9(3):308-11.
10. 10. Ba-bai-ke-re MM, Huang HG, Re WN, et al. World J Gastroenterol. 2011 Mar 21;17(11):1448-56.
11. 11. Gobet A. Med. Prat. 1978, (1-2), 713-714
12. 12. Garner RC, Garner JV, Gregory S, et al. J Pharm Sci. 2002 Jan;91(1):32-40
13. 13. Shoab SS, Porter JB, Scurr JH, et al. J Vasc Surg, 2000;31:456-61.
14. 14. Jiang ZM, Cao JD. Curr Med Res Opin. 2006 Jun;22(6):1141-7.
15. 15. Dimitroulopoulos D , Tsamakidis K, Xinopoulos D, et al. Clin Ther. 2005 Jun;27(6):74654.
16. 16. Misra MC , Parshad R. Br J Surg. 2000 Jul;87(7):86872.
17. 17. Diana G, Catanzaro M, Ferrara A, Ferrari P. Clin Ter. 2000 Sep-Oct;151(5):341-4.
18. 18. Buckshee K, Takkar D, Aggarwal N. Int J Gynaecol Obstet. 1997 May;57(2):145-51.
19. 19. Ho YH, Tan M, Seow-Choen F. Dis Colon Rectum. 2000 Jan;43(1):66-9.