Hematuria overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Steven C. Campbell, M.D., Ph.D. Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [2] Aida Javanbakht, M.D.
Overview
Presence of >5 red blood cells (RBCs) per high-power microscopic field in the urine is called hematuria. It can have either benign or malignant etiology. Patients with hematuria could be asymptomatic. Therefore, all patients presenting with a single episode of haematuria require urgent investigation. Microscopic hematuria, or microhematuria (MH), is defined as the presence of RBC on microscopic examination of the urine not evident on visual inspection of the urine. The prevalence of MH among healthy participants in screening studies is 6.5% (95% confidence interval [CI] 3.4 to 12.2), with higher rates in studies with a predominance of males, older patients, and smokers.
Definition
Hematuria is defined as the presence of blood in the urine.[1] Gross hematuria and microscopic hematuria( MH) are 2 types of hematuria. One of the most widely used definitions of microhematuria is the presence of at least two or three red blood cells per high power-field on a properly collected urinary specimen (confirmation should be done with 2 or 3 urinalyses taken consecutively) in the absence of an obvious benign cause (e.g. mild trauma or sexual activity preceding the collection). Urinary dipstick it lacks specificity for MH as it also detects myoglobin and free heme without the presence of any hematuria.[2]
Classification
Hematuria may be classified based on its source, visibility, duration, and pathophysiology.
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Pathophysiology
The pathophysiology of hematuria depends on the underlying etiology. It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB). Molecular defects (COL4A5, COL4A3/COL4A4, COL4A1, Non muscle myosin IIA heavy chain, Fibronectin, etc.) might be involved in the pathogenesis of glomerular hematuria. Gross pathology and microscopic pathology might differ depending on the underlying etiology of hematuria.
Causes
Causes of hematuria can range from benign conditions such as urinary tract infection to serious conditions such as bladder cancer.[3] Extrarenal site is responsible for more than 60% of cases of hematuria. Of these, the most important underlying disease is malignancy. In the primary care population, about 5% of patients with microscopic hematuria will have a urinary tract malignancy, mainly of the bladder or prostate. The most common nonmalignant causes of extrarenal hematuria are infections, such as cystitis, prostatitis, and urethritis.Regarding renal causes of microscopic hematuria, the most common cause of isolated glomerular hematuria (without significant proteinuria) is IgA nephropathy, followed by thin basement membrane disease, hereditary nephritis (Alport syndrome), and mild focal glomerulonephritis of other causes.[4] Resolvable or self-limited causes of hematuria include strenuous exercise, fever, medications, exposure to toxins (such as contrast dyes used in radiological procedures), physical injury to the kidney or bladder, menstrual or gynecological bleeding[5].
Differential Diagnosis
Gross hematuria(GH) must be distinguished from pigmenturia, which may be due to endogenous sources (e.g., bilirubin, myoglobin,and porphyrins), foods ingested (e.g., beets and rhubarb), drugs (e.g., phenazopyridine), and simple dehydration. This distinction can be made easily by urinalysis with microscopy. Notably, myoglobinuria and other factors can cause false-positive chemical tests for hemoglobin, so urine microscopy is required to confirm the diagnosis of hematuria. GH also must be distinguished from vaginal bleeding in women, which usually can be achieved by obtaining a careful menstrual history, collecting the specimen when the patient is not having menstrual or gynecologic bleeding, or, if necessary, obtaining a catheterized specimen. GH may also be detected by the presence of blood spotting on the undergarments of incontinent patients. After ruling out vaginal bleeding and mimics of hematuria, a urologic source must be suspected.
Epidemiology and Demographics
According to the American Urological Association (AUA) guidelines, the prevalence of hematuria ranging from 2100 to 31400 per 100,000 individuals. Asymptomatic hematuria is common in clinical practice, with a prevalence ranging from 0.18% to 38.7%.[6] Transient microscopic hematuria may occur in 6% to 39% of the population studied, but persistent microscopic hematuria in 3 or more consecutive urinalyses occurs less often, and is seen in 0.5% to 2% of the population under study. In the prevalence of underlying urinary tract disease, there is no clear difference between patients with transient microscopic hematuria and those with persistent microscopic hematuria.[7]
Risk Factors
Certain factors that increase the chance of hematuria include recent infection, strenuous exercise or normal exercise under extreme circumstances, males > 50 years old, and female sex (due to the higher prevalence of urinary tract infection). Common risk factors for urinary tract malignancy in patients with hematuria include age >35, analgesic abuse, exposure to chemicals or dyes (benzenes or aromatic amines), male sex, and smoking history.
Screening
There is insufficient evidence to recommend routine screening for bladder cancer in patients with hematuria. However, according to the recently developed scoring system known as Haematuria Cancer Risk Score (HCRS), screening for bladder cancer in patients with hematuria with high HCRS score (based on age, sex, smoking history, and type of hematuria) might be recommended.
Natural History, Complications and Prognosis
Natural history, complications, and prognosis of hematuria usually depend on the underlying etiology. Accompanying proteinuria might indicate significant kidney disease. The presence of proteinuria, hypertension, and/or abnormal renal function might be associated with a particularly poor prognosis among patients with hematuria. Isolated hematuria is associated with a good prognosis in children.
Diagnosis
History and Symptoms
History and symptoms of hematuria depends on the eitology. The history should also include an assessment of associated symptoms, such as gross hematuria, voiding symptoms, or flank pain. Patients' risk factors for known causes of hematuria also should be queried. It is important to know the patient's urologic history, particularly any surgeries or febrile UTIs. It is also critical to ask about the patient's general medical history, to identify potentially contributory diagnoses, such as hypertension, renal insufficiency, bleeding disorders, or sickle cell disease. Current medication use, including anticoagulants and antiplatelet therapies, should be elicited, along with recent coagulation values and any concomitant medications that would potentiate the effects of blood thinners. Family history of nephritis, polycystic kidneys, and rare familial tumor syndromes of the kidney (e.g., von Hippel-Lindau) or urothelium (e.g., Lynch syndrome) also may be informative.[8]
Physical Examination
Physical examination of the patient with MH should be focused on isolating the underlying cause. The physical examination findings will vary depending on the etiology, as follows:[9][2]
- Blood pressure, heart rate, respiration rate, temperature, and consciousness level are important to assess hemodynamic stability, volume status, and possible presence of shock or sepsis as the treatment of hematuria is driven by the underlying pathophysiology and is in large part conservative.
- Presence of hypertension may indicate advanced glomerulopathy.
- Skin and mucosal membrane examination are useful to check for signs of bleeding disorders, such as petechiae, purpura, ecchymoses, and gingival bleeding.
- Jugular venous distention indicates volume overload.
- Flank tenderness;
- Masses in the flank, abdomen, suprapubic area, or urethra
- Enlarged, nodular, tender, or fluctuant prostate.
- Bruising
- Fever
Diagnostic Evaluation
Specifically, among patients with GH, 50% have been found to have a demonstrable cause, with 20% to 25% found to have a urologic malignancy, most commonly bladder cancer and kidney cancer. Given the increased frequency with which clinically significant findings are associated with GH, the recommended evaluation in this setting is relatively uniform. That is, patients presenting with GH in the absence of antecedent trauma or culture-documented UTI should be evaluated with a urine cytologic examination, cystoscopy, and upper tract imaging, preferably CT urogram.
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Treatment
Medical Therapy
Treatment depends on the etiology of the hematuria and severity of symptoms. Controlling high blood pressure is usually the most important part of treatment.
Medicines that may be prescribed include:
- Blood pressure medications to control high blood pressure, most commonly angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
- Corticosteroids
- Medications that suppress the immune system
Surgery
Surgery for hematuria depends on the underlying etiology.
Prevention
There is no specific preventive methods for either hematuria or microscopic hematuria.
References
- ↑ Rew, Karl (2010). Primary care urology. Philadelphia, Pa. London: Saunders. ISBN 978-1437724899.
- ↑ 2.0 2.1 Davis R, Jones JS, Barocas DA, Castle EP, Lang EK, Leveillee RJ et al. (2012) Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol 188 (6 Suppl):2473-81. DOI:10.1016/j.juro.2012.09.078 PMID: 23098784
- ↑ Rew, Karl (2010). Primary care urology. Philadelphia, Pa. London: Saunders. ISBN 978-1437724899.
- ↑ Rew, Karl (2010). Primary care urology. Philadelphia, Pa. London: Saunders. ISBN 978-1437724899.
- ↑ Blood in Urine (Hematuria). American Association for Clinical Chemistry (2020). Available at https://labtestsonline.org/conditions/blood-urine-hematuria. Accessed on April 14, 2020
- ↑ Loo RK, Lieberman SF, Slezak JM, Landa HM, Mariani AJ, Nicolaisen G et al. (2013) Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria. Mayo Clin Proc 88 (2):129-38. DOI:10.1016/j.mayocp.2012.10.004 PMID: 23312369
- ↑ Rew, Karl (2010). Primary care urology. Philadelphia, Pa. London: Saunders. ISBN 978-1437724899.
- ↑ Wein, Alan (2016). Campbell-Walsh urology. Philadelphia, PA: Elsevier. ISBN 978-1455775675.
- ↑ Cohen RA, Brown RS (2003) Clinical practice. Microscopic hematuria. N Engl J Med 348 (23):2330-8. DOI:10.1056/NEJMcp012694 PMID: 12788998