|Hematuria (Differential diagnosis)|
|Other names||Haematuria, erythrocyturia, blood in the urine|
|Visible hematuria that is tea-colored|
|Symptoms||Blood in the urine|
|Causes||Urinary tract infection, kidney stone, bladder cancer, kidney cancer|
Hematuria or haematuria is defined as the occurrence of blood or red blood cells in the urine. The word hematuria is derived from Greek haima (αἷμα) "blood" and ouron (οὖρον) "urine". Hematuria can be visible to the naked eye (termed "gross hematuria") and may appear red or brown (sometimes referred to as tea-colored), or it can be microscopic (i.e. not visible to the eye but detected with a microscope or laboratory test). The origin of the blood that enters and mixes with the urine can arise from any anatomical site within the urinary system, including the kidney, ureter, urinary bladder, and urethra, and in men, the prostate. Common causes of hematuria include urinary tract infection (UTI), kidney stones, viral illness, trauma, bladder cancer, and exercise. The underlying causes of hematuria can be divided into glomerular and non-glomerular causes, referring to the involvement of the glomerulus of the kidney. Notably, not all red urine is hematuria. Other substances such as certain medications and foods (e.g. blackberries, beets, food dyes) can cause urine to appear red. Menstruation in women may also cause the appearance of hematuria and may result in a positive urine dipstick test for hematuria. Additionally, a urine dipstick test may be falsely positive for hematuria due to other substances in the urine such as myoglobin during rhabdomyolysis. A positive urine dipstick test should be confirmed with microscopy, where hematuria is defined by three of more red blood cells per high power field. When hematuria is detected, a thorough history and physical examination with appropriate further evaluation (e.g. laboratory testing) can help determine the underlying cause.
- In terms of the visibility, hematuria can be visible to the naked eye (termed "gross hematuria") and may appear red or brown (sometimes referred to as tea-colored), or it can be microscopic (i.e. not visible to the eye but detected with a microscope or laboratory test). Microscopic hematuria is present when there are three of more red blood cells per high power field.
- In terms of the anatomical origin, blood or red blood cells can enter and mix with urine at multiple anatomical sites within the urinary system, including the kidney, ureter, urinary bladder, and urethra, and in men, the prostate. Additionally, menstruation in women may cause the appearance of hematuria and may result in a positive urine dipstick test for hematuria. The causes corresponding to these anatomic locations can be divided into glomerular and non-glomerular causes, referring to the involvement of the glomerulus of the kidney. Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes.
- In terms of the timing during urination, hematuria can be initial, terminal or total, meaning blood can appear in the urine at the onset, midstream, or later. If it appears soon after the onset of urination, a distal site is suggested. A longer delay suggests a more proximal lesion. In other words, shorter times suggest distal sites while longer times suggest proximal sites. Hematuria that occurs throughout urination suggests that bleeding is occurring above the level of the bladder.
Glomerular causes include:
- IgA nephropathy
- Thin glomerular basement membrane disease
- Hereditary nephritis (Alport's disease)
- Hemolytic uremic syndrome
- Postinfectious glomerulonephritis
- Membranoproliferative glomerulonephritis
- Lupus nephritis
- Henoch-Shonlein purpura
- Nephritic syndrome
- Nephrotic syndrome
- Polycystic kidney disease
- Idiopathic hematuria
Visible blood clots in the urine indicate a non-glomerular cause. Non-glomerular causes include:
- Urinary tract infections, such as pyelonephritis, cystitis, prostatitis, and urethritis
- Kidney stones
- Cancers, such as renal cell carcinoma and bladder cancer, and in men, prostate cancer
- Urinary tract strictures
- Benign prostatic hyperplasia
- Renal papillary necrosis
- Trauma or damage to the lining of the urinary tract
- Intense exercise
- Increased tendency to bleed due to acquired or genetic conditions (e.g. sickle cell disease or vitamin K deficiency bleeding) or certain medications (e.g. blood thinners)
Mimickers of hematuria
Medications that may cause urine to appear red include:
Foods that may cause urine to appear red include:
False positive urine dipstick
A urine dipstick may be falsely positive for hematuria due to other substances in the urine. While the urine dipstick test is able to recognize heme in red blood cells, it also identifies free hemoglobin and myoglobin. Free hemoglobin may be found in the urine resulting from hemolysis, and myoglobin may be found in the urine resulting from rhabdomyolysis. Thus, a positive dipstick test does not necessarily indicate hematuria; rather, microscopy of the urine showing three of more red blood cells per high power field confirms hematuria.
In women, menstruation may cause the appearance of hematuria and may result in a urine dipstick test positive for hematuria. Menstruation can be ruled out as a cause of hematuria by inquiring about menstruation history and ensuring the urine specimen is collected without menstrual blood.
The evaluation of hematuria is dependent upon the visibility of the blood in the urine (i.e. visible/gross vs microscopic hematuria). Visible hematuria must be investigated, as it is due to a pathological cause. In those with visible hematuria, urological cancer (most frequently bladder or kidney cancer) is discovered in 20-25%. Hematuria alone without accompanying symptoms should be raise suspicion of malignancy of the urinary tract until proven otherwise.
The first step in evaluation of red or brown colored urine is to confirm true hematuria with urinalysis and urine microscopy, where hematuria is defined by three of more red blood cells per high power field. Although a urine dipstick test may be used, it can give false positive or false negative results. In gathering information, it is important to inquire about recent trauma, urologic procedures, menses, and culture-documented urinary tract infection. If any of these are present, it is appropriate to repeat a urinalysis with urine microscopy in 1 to 2 weeks or after treatment of the infection. If the results of the urinalysis and urine microscopy reveal a glomerular origin of hematuria (indicated by proteinuria or red blood cell casts), consultation of a nephrologist should be made. If the results of the urinalysis indicate a non-glomerular origin, a microbiological culture of the urine should be performed, if it has not been done already. If the culture is positive, treatment of the infection should follow and urinalysis and urine microscopy should be repeated once complete. If the culture is negative or if hematuria persists after treatment, CT urogram and cystoscopy should be performed. Of note, hemodynamic stability should be monitored and a complete blood count should be ordered to assess for anemia.
In summary, those with visible hematuria confirmed by urinalysis and urine microscopy and with no recent trauma, urologic procedures, menses, or urinary tract infection should undergo cystoscopy and CT urogram.
After detecting and confirming hematuria with urinalysis and urine microscopy, the first step in evaluation of microscopic hematuria is to rule out benign causes. Benign causes include urinary tract infection, viral illness, kidney stone, recent intense exercise, menses, recent trauma, or recent urological procedure. After benign causes have resolved or been treated, a repeat urinalysis and urine microscopy is warranted to ensure cessation of hematuria. If hematuria persists (even if there is a suspected cause), the next step is to stratify the risk of the person for urothelial cancer into low, intermediate, or high risk to determine next steps. To be in the low risk category, one must satisfy all of the following criteria: Has never smoked tobacco or smoked less than 10 pack-years; is a female less than 50 years old or a male less than 40 years old; has 3-10 red blood cells per high power field; has not had microscopic hematuria before; and has no other risk factors for urothelial cancer. To be in the intermediate risk category, one must satisfy any of the following criteria: Has smoked 10-30 pack-years; is a female 50-59 years old or a male aged 40-59 years old; has 11-25 red blood cells per high power field; or was previously a low-risk patient with persistent microscopic hematuria and has 3-25 red blood cells per high power field. To be in the high risk category, one must satisfy any of the following criteria: Has smoked more than 30 pack-years; is older than 60 years of age; or has above 25 red blood cells per high power field on any urinalysis. For the low risk category, the next step is to either repeat a urinalysis with urine microscopy in 6 months or perform a cystoscopy and renal ultrasound. For the intermediate risk category, the next step is to perform a cystoscopy and renal ultrasound. For the high risk category, the next step is to perform a cystoscopy and CT urogram. If an underlying cause for hematuria is discovered, it should be managed appropriately. However, if no underlying cause is discovered, the hematuria should be re-evaluated with urinalysis and urine microscopy within 12 months. Additionally, for all risk categories, if a nephrologic origin is suspected, consultation of a nephrologist should be made.
The pathophysiology of hematuria can often be explained by damage to the structures of the urinary system, including the kidney, ureter, urinary bladder, and urethra, and in men, the prostate. Common mechanisms include structural disruption to the glomerular basement membrane and mechanical or chemical erosion of the mucosal surfaces of the genitourinary tract.
Medical emergency: Acute clot retention
Acute clot retention is one of three emergencies that can occur with hematuria. The other two are anemia and shock. Blood clots can prevent urine outflow through either ureter or the bladder. This is known as acute urinary retention.
Blood clots that remain in the bladder are digested by urinary urokinase producing fibrin fragments. These fibrin fragments are natural anticoagulants and promote ongoing bleeding from the urinary tract. Removing all blood clots prevents the formation of this natural anticoagulant. This in turns facilitates the cessation of bleeding from the urinary tract.
The acute management of obstructing clots is the placement of a large (22-24 French) urethral Foley catheter. Clots are evacuated with a Toomey syringe and saline irrigation. If this does not control the bleeding, management should escalate to continuous bladder irrigation (CBI) via a three-port urethral catheter. If both a large urethral Foley catheter and CBI fail, an urgent cystoscopy in the operating room will be necessary. Lastly, a transfusion and/or a correction of a coexisting coagulopathy may be necessary.
In the United States of America, microscopic hematuria has a prevalence of somewhere between 2% and 31%. Higher rates exist in individuals older than 60 years of age and those with a current or past history of smoking. Only a fraction of individuals with microhematuria are diagnosed with a urologic cancer. When asymptomatic populations are screened with dipstick and/or microscopy medical testing about 2% to 3% of those with hematuria have a urologic malignancy. Routine screening is not recommended. Individuals with risk factors who undergo repeated testing have higher rates of urologic malignancies. These risks factors include age (>35 years), male gender, previous or current smoking, chemical exposure (e.g., benzenes or aromatic amines), and prior pelvic radiation therapy.
In pediatric populations, the prevalence is 0.5–2%. Risks factor include older age and female gender. About 5% of individuals with microscopic hematuria receive a cancer diagnosis. 40% of individuals with macroscopic hematuria (blood easily visible in the urine) receive a cancer diagnosis.
Hematuria in children
Common causes of hematuria in children are:
- Strenuous exercise
- Acute nephritis
- Congenital abnormalities:
- Non-vascular: ureteropelvic junction obstruction, posterior urethral valves, urethral prolapse, urethral diverticula, multicystic dysplastic kidney
- Vascular: arteriovenous malformations, hereditary hemorrhagic telangiectasias, renal vascular thromboses.
- Urinary stones.
- Coagulation disorders.
- Mechanical trauma: masturbation, foreign body.
- Nephritic Syndrome: IgA nephropathy, Post-streptococcal glomerulonephritis, Benign familial hematuria, Alport syndrome.
- Sickle cell trait or disease.
- Saleem, Muhammad O.; Hamawy, Karim (2022), "Hematuria", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30480952, retrieved 2022-01-17
- Bolenz, Christian; Schröppel, Bernd; Eisenhardt, Andreas; J. Schmitz-Dräger, Bernd; Grimm, Marc-Oliver (November 2018). "The Investigation of Hematuria". Deutsches Ärzteblatt International. 115 (48): 801–807. doi:10.3238/arztebl.2018.0801. ISSN 1866-0452. PMC 6365675. PMID 30642428.
- Kirkpatrick, Wanda G. (1990), "Chapter 184 - Hematuria", in Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.), Clinical Methods: The History, Physical, and Laboratory Examinations. (3rd ed.), Boston: Butterworths, ISBN 978-0-409-90077-4, PMID 21250137, retrieved 2022-01-17
- Papadakis, Maxine A.; McPhee, Stephen J.; Rabow, Michael W. (14 September 2021). Current medical diagnosis & treatment 2022. 23-02: Hematuria. ISBN 978-1-264-26938-9. OCLC 1268130534.
- Charles M Wiener; Laura C Cappelli; Brian T Garibaldi; Catherine H Marshall; Brian Houstan; Sara C Keller, eds. (2018). Harrison's principles of internal medicine (20th ed.). New York. Chapter 48: Azotemia and Urinary Abnormalities. ISBN 978-1-259-64403-0. OCLC 1029074059.
- Stern, Scott D.C. Symptom to diagnosis: an evidence-based guide. Chapter 21-1: Approach to the Patient with Hematuria - Case 1. OCLC 1121597721.
- Alan W. Partin; Roger R. Dmochowski; Louis R. Kavoussi; Craig Peters, eds. (2021). "Evaluation and Management of Hematuria". Campbell-Walsh-Wein urology (Twelfth ed.). Philadelphia, PA. ISBN 978-0-323-54642-3. OCLC 1130700336.
- McAninch, Jack W.; Lue, Tom (2013). "Chapter 3: Symptoms of Disorders of the Genitourinary Tract". Smith & Tanagho's General Urology. McGraw-Hill Education.
- Hashmi, Mydah S.; Pandey, Jyotsna (2022), "Nephritic Syndrome", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32965911, retrieved 2022-01-19
- Izzo, Joseph L.; Sica, Domenic A.; Black, Henry Richard (2008). Hypertension Primer. Lippincott Williams & Wilkins. p. 382. ISBN 978-0-7817-8205-0.
- Davis, Rodney; Jones, J. Stephen; Barocas, Daniel A.; Castle, Erik P.; Lang, Erich K.; Leveillee, Raymond J.; Messing, Edward M.; Miller, Scott D.; Peterson, Andrew C.; Turk, Thomas M. T.; Weitzel, William (2012-12-01). "Diagnosis, Evaluation and Follow-Up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline". Journal of Urology. 188 (6S): 2473–2481. doi:10.1016/j.juro.2012.09.078. PMID 23098784.
- Barocas, Daniel A.; Boorjian, Stephen A.; Alvarez, Ronald D.; Downs, Tracy M.; Gross, Cary P.; Hamilton, Blake D.; Kobashi, Kathleen C.; Lipman, Robert R.; Lotan, Yair; Ng, Casey K.; Nielsen, Matthew E. (2020-10-01). "Microhematuria: AUA/SUFU Guideline". Journal of Urology. 204 (4): 778–786. doi:10.1097/JU.0000000000001297. PMID 32698717. S2CID 220717643.
- Kaplan, Damara, MD, PhD; Kohn, Taylor. "Urologic Emergencies: Gross Hematuria with Clot Retention". American Urological Association. Retrieved 2019-12-11.
- Coplen, D.E. (January 2013). "Diagnosis, Evaluation and Follow-Up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline". Yearbook of Urology. 2013: 1–2. doi:10.1016/j.yuro.2013.07.019. ISSN 0084-4071.
- Shah, Samir (2014). Step-up to pediatrics. Ronan, Jeanine C.; Alverson, Brian (First ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. pp. 175–176. ISBN 978-1451145809. OCLC 855779297.
- Cohen, Robert A.; Brown, Robert S. (2003-06-05). "Clinical practice. Microscopic hematuria". The New England Journal of Medicine. 348 (23): 2330–2338. doi:10.1056/NEJMcp012694. ISSN 1533-4406. PMID 12788998.
- Sharp, Victoria; Barnes, Kerri D.; Erickson, Bradley D. (December 1, 2013). "Assessment of Asymptomatic Microscopic Hematuria in Adults". American Family Physician. 88 (11): 747–54. PMID 24364522.
- Pade, Kathryn H.; Liu, Deborah R. (September 2014). "An evidence-based approach to the management of hematuria in children in the emergency department". Pediatric Emergency Medicine Practice. 11 (9): 1–13, quiz 14. ISSN 1549-9650. PMID 25296518.
Media related to Hematuria at Wikimedia Commons