Gross and Microscopic Hematuria

What is Gross and Microscopic Hematuria?

Hematuria is a condition where blood is found in the urine. This is a common issue in the field of urology, contributing to over 20% of all urological evaluations. There are various types of hematuria, including those that are sporadic or continuous, related or unrelated to kidney filtering units (glomeruli), and showing visible symptoms or not. The two primary classifications that are most clinically beneficial are gross hematuria, which is visible blood in the urine, and microhematuria, where red blood cells are detected in a urine test but are not visible to the naked eye.

In 2020, the American Urological Association brought in guidelines to diagnose microhematuria through microscopic evaluation. They suggested that if more than or equal to 3 red blood cells per high power microscopic field are seen in a urine sample, it could indicate this condition. These guidelines are necessary because abnormalities can often be missed if only urine dipsticks are used for the testing. The guidelines also stress the importance of excluding blood resulting from recent urological procedures, urinary tract infections, or rectal/vaginal bleeding. Studies suggest that better education about hematuria definitions could avoid unnecessary testing and referrals. Sometimes, it is recommended to have at least 2 or 3 confirmed microscopic findings of hematuria. When only a single instance of microscopic hematuria has been detected, it is advised to perform periodic urine examination for at least a year if no further investigation is carried out.

Microscopic hematuria can be further divided based on whether it shows symptoms, whether it is accompanied by protein in urine (which could indicate kidney disorders), or whether it occurs without protein in the urine (which could hint towards possible cancers in the urinary system). Microscopic urine analysis also helps to identify urinary infections and various substances that could be indicative of different diseases. If there aren’t any red blood cells visible in urine samples that tested positive in a dipstick test, it could suggest the presence of muscle proteins (myoglobinuria), blood proteins from ruptured red blood cells (hemoglobinuria), or other conditions leading to false-positive results. It is critical to confirm the dipstick test findings with microscopic examination of the urine sediment.

The most severe possible outcome of hematuria could be cancer. There are a variety of classification systems in place to sort patients into low-risk, medium-risk, and high-risk groups. One such reliable system is the 2020 American Urological Association Guideline on Microhematuria Risk Stratification Guide. It’s important to note that the majority of patients with true microhematuria are not referred to a urology specialist in a timely manner, potentially leading to delayed cancer diagnosis.

What Causes Gross and Microscopic Hematuria?

Hematuria is when you notice blood in your urine, which is often a symptom of genitourinary disorders or other diseases impacting your body. Understanding what’s causing the blood in your urine can be a bit tricky as there could be many potential sources. Doctors often categorize these sources as either glomerular or nonglomerular, although in some instances, they may not be able to pinpoint a definite cause. Protein in your urine is a common symptom of blood due to glomerular causes.

For infants and young children, the presence of blood in the urine might be a warning sign of several conditions or diseases. These might include Wilms tumor, polycystic kidney disease, Alport syndrome, inherited kidney inflammation, diseases like glomerulonephritis and hypercalciuria, urinary tract infections, or, in some instances, sickle cell disease, especially in Black children.

For older people, blood in the urine typically originates from urinary tract infections, kidney or bladder cancers, kidney stones, post-infection effects on the kidneys, trauma, prostate enlargement, or some medical procedures related to the urinary tract. Interestingly, about 50% of the time, doctors can’t point to a specific cause for the presence of blood in the urine.

When blood in the urine is accompanied by protein or casts (impressions of tiny tube-like structures called tubules) or abnormally shaped red blood cells, it often points towards some moderate kidney diseases. Some common kidney-related causes include Alport syndrome, various forms of kidney inflammation, Goodpasture syndrome, Henöch-Schonlein purpura, hypercalciuria, IgA nephropathy, lupus nephritis, minimal change disease, nephrotic syndrome, kidney disease after certain bacterial infections, and a thin basement membrane disease.

Nonglomerular causes for blood in the urine often show normal shapes of red blood cells under a microscope and usually don’t show signs of protein or casts in urine. Some of these causes could include bladder stones, prostate enlargement, urinary tract endometriosis, intense physical exercise, foreign bodies in the urinary tract like stones, catheters, and stents, injuries to the urinary tract during medical procedures, blood disorders like sickle cell anemia, condition of the bladder resulting in bleeding, infections, cancers of the kidney, bladder, and prostate, certain medications, kidney or bladder stones, a condition called Nutcracker Syndrome, a rare urinary bladder condition called Radiation cystitis, Schistosomiasis (a condition common in Africa and other endemic regions) and any injury affecting the urinary tract.

Risk Factors and Frequency for Gross and Microscopic Hematuria

Gross hematuria, or blood in urine, is a regular issue seen in outpatient clinics and emergency departments. A higher number of people experience asymptomatic hematuria or blood in the urine without symptoms. This type of hematuria can often go undetected for several years. It is particularly important to note that women’s evaluations for microhematuria – or small amounts of blood in the urine – are often delayed, which could potentially lead to worse outcomes for conditions like bladder and other urological cancers.

The occurrence of hematuria varies greatly depending on how it’s defined and whether or not medical evaluations are available. In the United States, it is estimated that 6.5% of the population will experience microscopic hematuria. This percentage can differ around the world, depending on the population studied and the definition of hematuria used. For instance, in Japan, where urine testing is a standard part of annual health check-ups, it was found that between 5% and 10% of the population tested positive for hematuria. Meanwhile, a meta-analysis showed that the prevalence of asymptomatic microhematuria ranged from as low as 0.19% to as high as 16%, with factors such as age and the population being studied influencing these numbers. In particular, older men were found to have an especially high prevalence of asymptomatic microhematuria, with some estimates as high as 21%.

When evaluating hematuria, the main goal is to identify and rule out any underlying cancers, as blood in the urine is often the first symptom of most bladder cancers. The overall chance of finding a genitourinary malignancy in patients with microscopic hematuria is around 3% but can rise to between 10% and 20% when there’s a large amount of blood in the urine (gross hematuria). This risk is even higher for certain groups, based on factors such as gender, age, smoking history, some chemical exposures, and the degree of blood in the urine. The American Cancer Society predicts there will be about 82,290 new cases of bladder cancer in 2023, with around 62,420 in men and 19,870 in women. The chance of bladder cancer in a year per 100,000 people is 18.7, albeit the overall incidence has been slowly decreasing. For kidney cancer, the estimated annual incidence in the US is around 79,000 cases (including approximately 50,000 in men and 29,000 in women), with 14,000 deaths. Globally, over 400,000 people are approximated to be diagnosed with kidney cancer annually, with around 180,000 deaths. Unfortunately, the overall incidence of kidney cancer appears to be slowly increasing.

The overall chance of glomerulonephritis, a type of kidney inflammation, has been recorded as high as 134 per 100,000 patient years, but it’s difficult to obtain reliable worldwide statistics. Kidney stone rates differ based on gender – they’re about twice as common in men as in women – ethnicity, and geographical location. The reported incidence of kidney stones varies, from between 7% and 13% in the US and Canada, 5% to 9% in Europe, and 1% to 5% in Asia. Urinary tract infections (UTIs) have a worldwide prevalence of around 0.7%, with risks increasing with age, previous UTI history, sexual activity, and diabetes. Acute cystitis, a type of UTI, is far more common than pyelonephritis – another type of UTI – as for every case of pyelonephritis, there are between 18 and 28 cases of acute cystitis. It’s important to note that while UTIs are a common cause of microhematuria, after UTI treatment, the resolution of microhematuria should still be confirmed, since UTIs and malignancies can coexist.

Benign prostatic hyperplasia (BPH) or a noncancerous increase in the size of the prostate is widespread but initially, most affected people display urinary symptoms other than blood in urine. Half the men older than 50 show some signs of BPH, a proportion that increases annually by about 2% to 2.5%. In the US, the chance of BPH in men aged 60 to 69 years is 70%, rising to over 80% in men older than 70 years. Polycystic kidney disease affects an estimated 4 to 7 million individuals worldwide and contributes to up to 15% of patients with end-stage kidney disease. Around 5% of all traumas involve the kidney, with the majority of such traumas caused by motor vehicle accidents, followed by sports injuries and falls.

Nutcracker syndrome, also known as left renal vein obstruction or entrapment, is a rare condition where the flow of blood from the left kidney to a large vein that carries blood back to the heart (the inferior vena cava) is blocked, often by a major artery (the superior mesenteric artery). The incidence of this condition is unknown but is most common in adults in their twenties and thirties. Asymptomatic blood in the urine is discovered in 4% of healthy school-aged children, noted more often in girls than boys.

Genetic diseases that cause hematuria are relatively rare. Alport syndrome, a genetic condition that causes kidney disease, hearing loss, and eye abnormalities, occurs more often in the US, where the incidence is estimated at 1 in 5,000 population, which equals up to 60,000 affected individuals. The incidence in Europe is lower, estimated at 1 in 50,000. Approximately 3% of all US children with end-stage kidney failure are diagnosed with Alport syndrome. Autosomal dominant polycystic kidney disease occurs approximately in 1 of every 1,000 live births. The occurrence of Goodpasture syndrome, a rare autoimmune disease that can affect the kidneys and lungs, is fewer than two cases per 1 million population. Thin basement membrane disease, a disorder that generally causes blood in urine but doesn’t often lead to serious health problems, is estimated to affect at least 1% of the global population. Some patients previously thought to have this condition were found to have variations of Alport Syndrome. Furthermore, sickle cell disease affects about 100,000 Black Americans, or 1 out of every 365 Black Americans, as per the Centers for Disease Control and Prevention. This can cause renal papillary necrosis or other kidney tissue death, resulting in microscopic hematuria. Sickle cell trait occurs in 1 out of every 12 babies of African ancestry born in the US.

In addition to the diseases and disorders mentioned, certain medications can cause blood in urine or urine discoloration. Medications such as allopurinol, blood thinners like warfarin or antiplatelet drugs, captopril, cephalosporins, chlorpromazine, cyclophosphamide, dichlorphenamide, furosemide, hydralazine, indinavir, ifosfamide, metronidazole, nitrofurantoin, phenazopyridine, phenolphthalein, minocycline, mirtazapine, penicillin, propylthiouracil, rifampin, senna, sulfa drugs, and thioridazine can all potentially lead to blood in urine.

• Allopurinol
• Blood thinners, such as warfarin or antiplatelet drugs
• Captopril
• Cephalosporins
• Chlorpromazine
• Cyclophosphamide
• Dichlorphenamide
• Furosemide
• Hydralazine
• Indinavir
• Ifosfamide
• Metronidazole
• Nitrofurantoin
• Phenazopyridine
• Phenolphthalein
• Minocycline
• Mirtazapine
• Penicillin
• Propylthiouracil
• Rifampin
• Senna
• Sulfa drugs
• Thioridazine

Signs and Symptoms of Gross and Microscopic Hematuria

Hematuria, or having blood in your urine, can be classified in two major ways. It can be either seen by the naked eye, thus referred to as “gross hematuria”, or only seen under a microscope, known as “microscopic hematuria”.

Gross hematuria is when you can see the blood in your urine. The urine may appear reddish or pink if there are issues in the lower part of your urinary system, or even brown or tea-colored due to certain chemical reactions. Sometimes, this can occur due to recently having urinary system surgery, a urinary infection, or passing a kidney stone. If you have this type of bloody urine without a known cause, doctors may need to do tests to rule out cancer risks, especially if you are over 35 years old.

Microscopic hematuria, on the other hand, can further be divided into:

• Asymptomatic: This is when blood cells in the urine are seen under a microscope, but the person isn’t showing symptoms. This type can sometimes be linked to urinary system cancers and often requires additional tests.
• Asymptomatic with proteinuria: This occurs when there’s protein in the urine of people showing no symptoms, which could suggest a condition called glomerulonephritis. Abnormally shaped red blood cells are usually spotted under the microscope. A more detailed investigation for this condition might be needed, including a possible kidney biopsy.
• Symptomatic: This is when the person has urinary symptoms like a frequent need to urinate, pain during urination, and others. This could be due to infections, prostate gland problems, or other urinary issues, and further examination is needed.

When doctors are examining you for possible hematuria, they may ask about additional symptoms, such as:

• Current menstrual cycle
• Back or side pain
• Unexplained weight loss, lack of appetite, weakness
• Unexplained fever
• Mass on your side
• Hearing loss
• Coughing up blood
• Joint pains, mouth sores, skin rash
• Swollen legs
• Lower abdominal pain
• Passage of urinary stones
• Recent skin or throat infection
• Urinary symptoms like pain during urination, urinating often, difficulty starting and stopping urination, and others

Doctors might also assess risk factors for developing urinary system cancers, such as:

• The amount and persistence of blood in your urine
• Family history of specific genetic syndromes or urinary system cancers
• Prior exposure to radiation therapy in the pelvic area
• Unexplained visible blood in urine
• Age, especially if above 60 years old
• Long-term use of urinary catheters
• Urinary symptoms
• Being a male
• Exposure at work to certain dangerous chemicals
• Prior exposure to specific chemotherapy drugs
• A history of heavy smoking

During the physical exam, your doctor will look for signs such as:

• Tenderness in the area above your kidneys
• Swelling of your legs
• Fever
• Mass or tenderness on your side
• Women-specific issues
• Hearing problems
• High blood pressure
• Swollen joints
• Enlarged lymph nodes
• Blood around the urinary opening or other abnormalities
• Enlarged or cyst-filled kidneys that can be felt
• Swelling around your eyes
• Paleness, jaundice, mouth sores, or rashes
• Tenderness above your pubic bone
• Discharge, injury, or tear from your urethra or vagina
• Vaginal bleeding

Testing for Gross and Microscopic Hematuria

Summarized: Often, the evaluation of hematuria, which is the presence of blood in urine, isn’t properly done. More than half the time, patients with hematuria don’t receive an adequate follow-up or referral to a urologist. A test known as cystoscopy is often not used as much as it should be, with doctors sometimes relying too heavily on diagnostic scans alone. Most of the hematuria caused by cancers, particularly bladder neoplasms, are best diagnosed using a cystoscopy.

One straightforward test to detect hematuria is a urine analysis. The presence of 3 or more red blood cells per high power field during a microscopic review of your urine is seen as a confirmed diagnosis. However, other findings in a urine test such as abnormal color or pH level, too much protein, white blood cells, bacteria, or crystals can help identify the source of hematuria.

The inability to identify a cause of hematuria suggests that further evaluation might be needed, such as checking for urinary tract infection, bladder or kidney cancer, kidney stones, bleeding from the prostate in older men, or traumatic injury.

For diagnosis and treatment of lower-risk patients with hematuria, potential strategies can involve repeating a urine test after 6 months or doing an ultrasound of the kidney area and a cystoscopy. If the symptoms continue, then a computed tomography test of the kidneys and bladder or ureter x-ray might be considered.

For intermediate or high-risk patients, a more comprehensive evaluation involving different types of tests and scans may be needed, including a CT scan and cystoscopy. However, any treatment or follow-up activities will depend on the specific findings.

The evaluation of hematuria, especially microscopic hematuria (where blood in urine is only visible under a microscope), is often delayed in women, where it is often considered to be due to a urinary tract infection, menstrual contamination, or bleeding from the vagina. This can lead to worse outcomes for bladder and other cancers of the urinary system in women.

Various scoring systems or biomarkers and cytology are not usually recommended for the initial evaluation of patients with microscopic hematuria because of their high false negative rates and unproven benefit in randomised trials. However, if a urinary biomarker test is done and shows a positive result, the patient should be treated as higher risk, and further tests are recommended.

Hematuria in children rarely occurs due to an underlying cancer. When a specific cause is identified, the most common diagnoses are glomerulonephritis conditions (where the kidneys’ filtering units are damaged), urinary tract infections, or hypercalciuria (a condition characterized by high levels of calcium in urine).

Treatment Options for Gross and Microscopic Hematuria

If you notice blood in your urine, sometimes called hematuria, it’s critical to find the underlying cause and determine the best course of action. In some cases, where it only happens occasionally, doesn’t affect kidney function, and blood tests and scans are normal, monitoring the situation might be enough. On the other hand, if the bleeding is significant and continuous, prompt management is necessary to ensure blood circulation stability. This could involve blood transfusions or medications to correct any underlying blood disorders. In severe cases, a procedure might be required to stop life-threatening bleeding from the kidney or when standard treatments don’t work for a condition known as hemorrhagic cystitis.

Sometimes, heavy bleeding could cause urinary difficulties or the passage of clots. In such cases, prompt treatment involving the insertion of a large catheter and continuous bladder irrigation (rinsing out the bladder) is necessary. If clot formations are not removed fully, the catheter could become blocked, and the blood clot breakdown products could actually prolong the bleeding. In these cases, additional treatments might be necessary, involving the use of certain substances to dissolve clots and avoid surgery.

For people with long-lasting or otherwise untreatable hematuria, various treatments might be necessary. In certain cases, radiation therapy could be beneficial. Severe bleeding originating from the bladder, especially after pelvic radiation treatments or certain chemotherapy drugs, can be challenging to manage. Treatments usually start with the least invasive approach and progress as necessary, potentially including surgical options.

Management of what’s called nonglomerular hematuria depends on the cause. For example, for urinary tract infections, antibiotics are prescribed. Certain conditions may require more specific treatments, some potentially involving surgery. Bleeding from the prostate can usually be controlled with standard procedures and treatments. If that’s not adequate, some other treatments might be considered.

When it comes to the management of glomerular hematuria, which is related to abnormalities in the kidney’s filtration system, it also depends on the specific cause and the effect on kidney function. Some hereditary conditions and autoimmune disorders require specific treatments. In addition to medications to help control blood pressure, reduce protein in the urine, and slow down the disease’s progression, some conditions might need additional treatments such as steroids, immunosuppressants, or rituximab, a drug used to treat autoimmune disorders.

Ultimately, the treatment for blood in the urine will depend on the underlying cause, and in some cases, more than one treatment approach might be necessary. It’s crucial to get an accurate diagnosis and work closely with your doctor to establish the best course of action for your specific case.

What else can Gross and Microscopic Hematuria be?

If you notice a change in your urine color to red, pink, brown, or yellow, it could be due to several causes, not just blood in the urine. Some of these can be:

• Alkaptonuria: a rare genetic disorder affecting how the body breaks down tyrosine, an amino acid.
• Bile pigments in urine: sometimes caused by liver disease.
• Drug effects: certain drugs can change the color of your urine.
• False positive urine dipstick test not confirmed by microscopy: sometimes, test mistakes can show blood in urine when there isn’t any.
• Hemoglobinuria: presence of hemoglobin, a protein in your red blood cells, could turn your urine red or brown.
• Hemolytic anemias: a group of conditions that cause your red blood cells to break down earlier than they should.
• Porphyria: a group of rare genetic diseases that can affect your nervous system or your skin.
• Rhabdomyolysis: a severe condition caused by damaged muscle tissue releasing its contents into your blood.
• Phenazopyridine use: a medication used for urinary tract discomfort that can turn your urine into a bright orange color.
• Various foods: foods like beets, blackberries, and fava beans can color your urine.

What to expect with Gross and Microscopic Hematuria

Children usually recover well from isolated hematuria, which is a condition where there’s blood in the urine. However, if this is accompanied by proteinuria (excess protein in the urine), high blood pressure, or abnormal kidney function, it could indicate a problem with the glomeruli (tiny filtering units in the kidneys) and might make prognosis more uncertain.

Unexplained blood in the urine, particularly if it’s visible to the naked eye, should be taken seriously in adults. This is because it could be a sign of cancer in the urinary tract. The outlook is usually positive for non-glomerular hematuria – when the blood in the urine isn’t coming from the glomeruli in the kidneys – because most causes for this can be specifically identified and treated.

Treatment options are limited and often less effective for genetic kidney diseases known as glomerulopathies. These diseases can get worse over time and could eventually result in kidney failure. Thin basement membrane disease, previously known as benign familial hematuria, has a very good outlook and usually doesn’t need specific treatment.

Early diagnosis and the best possible therapy can help prevent serious outcomes and maintain kidney function.

Possible Complications When Diagnosed with Gross and Microscopic Hematuria

If your urine contains blood, you may face some complications:

• You may receive a false positive result if you don’t use microscopic urine analysis to confirm positive dipstick findings for blood in urine. This may lead to expensive and unnecessary medical consultations and evaluations.
• If blood in urine is not diagnosed and treated correctly, it may lead to critical or life-threatening diseases.
• Certain conditions might cause the gradual loss of kidney function, often progressing to end-stage kidney failure.
• Even in severe cases, patients can be given dialysis or a kidney transplant, but these treatments might also have complications afterwards, such as infection, wound breaking open, and the body rejecting the new organ.

Recovery from Gross and Microscopic Hematuria

In terms of managing ongoing blood in the urine, or hematuria, there are a few important things to remember:

A diet low in salt is usually advised for patients who have high blood pressure and hematuria. This is because too much salt can raise the blood pressure further and worsen the hematuria.

Doctors often recommend cholesterol-lowering medications called ‘statins’ for patients with a kidney condition known as glomerulonephritis. These statins can help manage high blood pressure and slow down the hardening of the arteries, a condition known as atherosclerosis.

Also, it’s necessary to regularly monitor and test patients with different causes of hematuria. This helps to track the condition and assess the effectiveness of the treatment given.

Preventing Gross and Microscopic Hematuria

Hematuria refers to the presence of blood in the urine, which is a common issue. It can sometimes signal potential health problems such as kidney stones (urinary calculi) or cancerous tumors (malignancies). However, most times, further testing does not reveal any alarming issues, and this should be taken as a good sign. Doctors use a particular standard to determine whether further testing is needed: if there are 3 or more red blood cells per high power field (a measurement used in a microscopic urine test), they will consider further evaluation. This guideline is followed to prevent unnecessary tests and to reduce the patient’s worry.