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Urology & Nephrology Center, Mansoura University, Egypt
HAEMATURIA
A Challenging Medical Problem
ByBy
TAREK MEDHAT ABBAS,TAREK MEDHAT ABBAS, MDMDLecturer of NephrologyLecturer of Nephrology
Urology & Nephrology CenterUrology & Nephrology CenterMansoura UniversityMansoura University
EgyptEgypt
Urology & Nephrology Center, Mansoura University, Egypt
Definitions:
Normally the number of RBCs in urine should not be more than 5 RBCs/ high power field on microscopic examination of fresh centrifuged urine sample.
Haematuria
So, haematuria is defined as a secretion of more than 5 RBCs/ HPF in urine.
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Detection & quantificationDetection & quantificationof hematuriaof hematuria
Detection & quantificationDetection & quantificationof hematuriaof hematuria
Screening test ( dipsticks )Screening test ( dipsticks ) - 0.02-0.03 mg/dL of Hb, myoglobin- 0.02-0.03 mg/dL of Hb, myoglobin - ~5-20 RBC/mm³- ~5-20 RBC/mm³
Semiquantitative estimationSemiquantitative estimation - centrifugation of 10-15 ml of urine- centrifugation of 10-15 ml of urine - resuspention of sediment in 1 ml of - resuspention of sediment in 1 ml of residual urineresidual urine - high-power microscopy- high-power microscopy
Counting chamberCounting chamber – – the number of cells in 1 microliter of unspun the number of cells in 1 microliter of unspun
urineurine
Urology & Nephrology Center, Mansoura University, Egypt
Classification of hematuriaClassification of hematuria
Macroscopic - MicroscopicMacroscopic - Microscopic
Symptomatic - SymptomlessSymptomatic - Symptomless
Transient - PersistentTransient - Persistent
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Haematuria may be the only symptom or may be associated with other manifestations, according to the cause e.g. loin pain and fever with infection and renal colic with renal stones.
Haematuria could be gross (causing red-coloured urine) or microscopic (urine appears normal but RBCs are seen on microscopic examination). In gross hematuria, urine looks red if alkaline, but brown or coca-cola like if urine is acidic due to denaturation of the hemoglobin.
Urology & Nephrology Center, Mansoura University, Egypt
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Urology & Nephrology Center, Mansoura University, Egypt
HematuriaHematuriaHematuriaHematuria
Transient phenomenonof little significance
Transient phenomenonof little significance
Sign of seriousrenal disease
Sign of seriousrenal disease
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Causes of HematuriaCauses of HematuriaCauses of HematuriaCauses of Hematuria
Kidney diseaseKidney disease
Lesions along the urinary tractLesions along the urinary tract
Conditions unrelated to kidney and Conditions unrelated to kidney and urinary tracturinary tract www.MansFans.com
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
First: PRE-RENALFirst: PRE-RENAL
Hemorrhagic blood diseaseHemorrhagic blood disease
Sickle cell anemiaSickle cell anemia
Malignant hypertensionMalignant hypertension
Use of anticoagulantUse of anticoagulant
Liver diseaseLiver disease www.Man
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Urology & Nephrology Center, Mansoura University, Egypt
Haematuria of renal origin:
I. Glomerular haematuria:
Primary glomerular disease (e.g. IgA nephropathy, mesangial proliferative glomerulonephritis or crescentic glomerulonephritis)
Secondary glomerulonephritis i.e. renal involvement is a part of systemic disease
(e.g. post-strephococcal glomerulonephritis, Henoch-Schönlein purpura, SLE, polyarteritis nodosa).
Urology & Nephrology Center, Mansoura University, Egypt
b. Renal infection and tubulointerstitial diseases: Pyelonephritis, renal papillary necrosis, tuberculosis, and toxic nephropathies.
c. Stone disease, idiopathic hypercalciuriad. Renal neplastic diseases: Renal cell
carcinoma, transitional cell carcinoma of the renal pelvis and others.
e. Hereditary renal diseases: Modularly, sponge kidney, polycystic kidney disease, Alport’s syndrome, and thin basement membrane disease.
Urology & Nephrology Center, Mansoura University, Egypt
f. Loin-pain haematuria syndrome.
g. Coagulation defect: use of anticoagulant, liver disease and thrombocytopaenia.
h. Renal vascular disease: Renal infarction, renal vein thrombosis or malignant hypertension.
i. Exertional haematuria.www.MansFans.com
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Nephrolithiasis. Malignancy.
Ureteral inflammatory condition secondary to nearby inflammation e.g. diverticulitis, appendicitis or salpingitis.
Ureteral trauma e.g. during ureteroscopy.
Ureteral varices, aneurysms, or arteriovenous malformation.
Haematuria of ureteral origin:
Urology & Nephrology Center, Mansoura University, Egypt
a. Infection: schistosoma, viral or bacterial cystitis.
b. Neoplasm.
c. Foreign body in the bladder e.g. stones.
d. Trauma: During instrumentation or accidental.
e. Drug: e.g. cyclophosphamide induced haemorrhagic cystitis.
Haematuria of bladder origin:
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a. Urethritis: foreign body or local trauma to the urethra.
b. Prostate: Acute prostatitis, benign prostatic hypertrophy.
Hematuria of urethral (or associated
structures) origin:
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Acute nephritic syndromeAcute nephritic syndrome Acute nephritic syndromeAcute nephritic syndrome
Hematuria Hematuria
Proteinuria Proteinuria
Reduced renal functionReduced renal functionEdemaEdema
HypertensionHypertension
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Idiopathic Idiopathic HypercalciuriaHypercalciuria
Idiopathic Idiopathic HypercalciuriaHypercalciuria
Definition:Definition: Calcium excretion > 4 Calcium excretion > 4 mg/kg/daymg/kg/day
Urinary Ca/Creatinine > 0.2Urinary Ca/Creatinine > 0.2
Possible mechanism of hematuria:Possible mechanism of hematuria: microcrystals damaging the tubular or microcrystals damaging the tubular or mucosal epithelia. Resolution of mucosal epithelia. Resolution of hematuria with anticalciuric therapyhematuria with anticalciuric therapy
Urology & Nephrology Center, Mansoura University, Egypt
Alport syndromeAlport syndrome- hereditary disorder of GBM- hereditary disorder of GBM
X-linked dominantX-linked dominant
Autosomal recessiveAutosomal recessive
Autosomal dominantAutosomal dominant ww
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Urology & Nephrology Center, Mansoura University, Egypt
Renal diseaseRenal disease
Macro /MicrohematuriaMacro /Microhematuria
ProteinuriaProteinuria
Nephrotic syndromeNephrotic syndrome
HypertensionHypertension
Renal failure- malesRenal failure- males
Progressive or juvenile – 20 yProgressive or juvenile – 20 y
Nonprogressive – 40 yNonprogressive – 40 y
Urology & Nephrology Center, Mansoura University, Egypt
Hearing defectsHearing defects
Sensorineural bilateralSensorineural bilateral
Never congenitalNever congenital
Boys- 85% . Girls – 18% < 15yBoys- 85% . Girls – 18% < 15y
Progression of hearing loss parallels Progression of hearing loss parallels renal impairmentrenal impairment
Urology & Nephrology Center, Mansoura University, Egypt
Diagnosis of Alport syndromeDiagnosis of Alport syndrome
Hematuria with or without proteinuriaHematuria with or without proteinuria
HypertensionHypertension
Renal failureRenal failure
Ocular defects – anterior lenticonusOcular defects – anterior lenticonus
Familial hematuriaFamilial hematuria
Sensorineural hearing lossSensorineural hearing loss
Progression to renal failure occurring Progression to renal failure occurring in at least one affected subjectin at least one affected subject
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
ALPORT’S SYNDROME
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Familial benign essential Familial benign essential hematuriahematuria
Familial hematuria without Familial hematuria without proteinuria and without progression proteinuria and without progression to renal failure or hearing defectto renal failure or hearing defect
Diffuse attenuation of the GBM is Diffuse attenuation of the GBM is usually considered the hallmark of usually considered the hallmark of the conditionthe condition
It’s non pathognomonic of FBEHIt’s non pathognomonic of FBEH
Urology & Nephrology Center, Mansoura University, Egypt
ContinueContinue
Autosomal dominant traitAutosomal dominant trait
Normal antigenicity of the GBMNormal antigenicity of the GBM
Urology & Nephrology Center, Mansoura University, Egypt
Thin basement membrane Thin basement membrane nephropathynephropathy
HematuriaHematuria
ProteinuriaProteinuria
Attenuation of the GBMAttenuation of the GBM
In children may be AlportIn children may be Alport
In adults m/p benign disorderIn adults m/p benign disorder
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Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
HEREDITARY NEPHROPATHYHEREDITARY NEPHROPATHYHEREDITARY NEPHROPATHYHEREDITARY NEPHROPATHY
Benign Familial Hematuria
Alport Syndrome
Overlap of histological findingsOverlap of histological findings
The prognosis appears to be depend more on the degree of clinical expression in other members of the family and less
on the histological findings
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
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Urology & Nephrology Center, Mansoura University, Egypt
Hematuria not representing kidney Hematuria not representing kidney or urinary tract disorderor urinary tract disorder
Hematuria not representing kidney Hematuria not representing kidney or urinary tract disorderor urinary tract disorder
Following exerciseFollowing exercise
Febrile disorders Febrile disorders
Gastroenteritis with dehydrationGastroenteritis with dehydration
Contamination from external Contamination from external genitaliagenitalia
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Transient microscopic haematuria is relatively common. Up to 39% of adults between ages of 18 and 33 may have microscopic haematuria at least once, and up to 16% may have it in two or more occasions. Therefore, an extensive workup is not warranted except in high-risk patients, > 50 years of age and those patients with other clinical or urinary abnormalities.
Urology & Nephrology Center, Mansoura University, Egypt
Initial is usually urethral.
Terminal hematuria is usually prostatic or bladder origin.
Total hematuria is either bladder ureteral or renal origin.
Patterns Of Haematuria
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Differential Diagnosis of Haematuria:A. First, haematuria should be differentiated
from other causes of red or brownish urine:Dipsticks (Hemastix) will be positive with
haematuria, hemoglobinuria (hemolysis) and with myoglobinuria (muscle damage) but negative with other causes e.g. prophyrins (in porphyria), bile (in jaundice), melanin (in melanoma), alkaptonuria, food dyes and drugs as PAS or phenylphthalein.
Microscopy will show RBC’s only with haematuria.
Urology & Nephrology Center, Mansoura University, Egypt
False positive test for haematuria:
Haemoglobinuria.
Myoglobinuria.
Ascorbic acid.
False negative test for hematuria:
Highly diluted urine.
Urology & Nephrology Center, Mansoura University, Egypt
Haematuria could be glomerular (because of glomerular disease, sometimes called medical); or non glomerular (sometimes called surgical).
1. The shape of RBCs in urine are small and dysmorphic in cases with glomerular haematuria while it will be normal in case of non glomerular haematuria.
Glomerular haematuria could be differentiated from non glomerular haematuria by:
Urology & Nephrology Center, Mansoura University, Egypt
2. Means corpuscular volume of RBCs in urine of patient with glomerular haematuria is smaller (< 72 FL) than that in peripheral blood, but in non glomerular cases is equal.
3. Proteinuria is present in most cases of glomerular hematuria but not in cases of non glomerular hematuria.
4. Casts, especially red cell casts are seen in glomerular haematuria.
5. Blood clots indicate non-glomerular bleeding and can be associated with pain & colic.
6. Three-glass test.
Urology & Nephrology Center, Mansoura University, Egypt
Glomerular versus extraglomerular Glomerular versus extraglomerular bleedingbleeding
Urinary findingUrinary finding GlomerularGlomerular ExtraglomerularExtraglomerular
Red cell castsRed cell casts May be presentMay be present AbsentAbsent
Red cell Red cell morphologymorphology
DysmorphicDysmorphic UniformUniform
ProteinuriaProteinuria May be presentMay be present AbsentAbsent
ClotsClots AbsentAbsent May be presentMay be present
ColorColor May be red or May be red or brownbrown
May be redMay be red
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Isolated HematuriaIsolated Hematuria(microscopic)(microscopic)
Isolated HematuriaIsolated Hematuria(microscopic)(microscopic)
No other urinary abnormalitiesNo other urinary abnormalities
No renal insufficiencyNo renal insufficiency
No evidence for systemic diseaseNo evidence for systemic disease
Incidence ( school-aged children )Incidence ( school-aged children )
4-6% - single urine examination4-6% - single urine examination
0.5-1% - repeated testing over 6-12 0.5-1% - repeated testing over 6-12 monthsmonths
Urology & Nephrology Center, Mansoura University, Egypt
Etiologies of isolated HematuriaEtiologies of isolated HematuriaEtiologies of isolated HematuriaEtiologies of isolated Hematuria
GlomerularGlomerular - - Benign Recurrent or Persistent Hematuria Benign Recurrent or Persistent Hematuria 1.Sporadic1.Sporadic 2.Familial2.Familial - IgA Nephropathy- IgA Nephropathy - Alport syndrome- Alport syndrome - PSAGN- PSAGN
Non-glomerularNon-glomerular - Idiopathic Hypercalciuria- Idiopathic Hypercalciuria - Cystic Kidneys- Cystic Kidneys - Urinary Tract obstruction- Urinary Tract obstruction - Tumors- Tumors - Trauma- Trauma
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Hematuria with familial associationHematuria with familial associationHematuria with familial associationHematuria with familial association
GlomerularGlomerular - Benign Familial Hematuria - Benign Familial Hematuria - Alport syndrome- Alport syndrome
Non-glomerularNon-glomerular
- Idiopathic Hypercalciuria- Idiopathic Hypercalciuria - Polycystic Kidney Disease- Polycystic Kidney Disease - Urolithiasis- Urolithiasis - Tumors- Tumors
Urology & Nephrology Center, Mansoura University, Egypt
First exclude haemoglobinuria and myoglobinuria since both of them can also cause positive dipstick test for haematuria. This is done by microscopic examination of fresh urine sample. In case of haematuria, RBCs could be seen while in the other two conditions no RBC’s could be seen.
Approach to a case of haematuria
Urology & Nephrology Center, Mansoura University, Egypt
In case of myoglobinuria, clinical examination may show manifestations of muscle disease and the examination of urine by immunoelectrophoresis may show myoglobin.
In case of haemoglobinuria, manifestations of haemolysis may be evident
Urology & Nephrology Center, Mansoura University, Egypt
Evaluation of HematuriaEvaluation of Hematuria HistoryHistory
Evaluation of HematuriaEvaluation of Hematuria HistoryHistory
Detailed review of family historyDetailed review of family history hematuriahematuria proteinuriaproteinuria renal insufficiencyrenal insufficiency deafnessdeafness stonesstones
Precipitating factorsPrecipitating factors infectioninfection exerciseexercise
Abdominal painAbdominal pain HSPHSP hydronephrosishydronephrosis pyelonephritispyelonephritis urolithiasisurolithiasis
Urology & Nephrology Center, Mansoura University, Egypt
History Taking History Taking
Past history Past history (( previous episodes, recent previous episodes, recent food and drug ingestion, exercise, food and drug ingestion, exercise, instrumentation, menstruation…instrumentation, menstruation… ))
Dysuria ? Dysuria ? Associated bladder irritability or flank pain ?Associated bladder irritability or flank pain ?
Time of hematuriaTime of hematuria initial:initial: urethritis, stricture, meatal stenosisurethritis, stricture, meatal stenosis total:total: bladder, ureter, kidneybladder, ureter, kidney terminal:terminal: bladder neck or prostatic urethrabladder neck or prostatic urethra
Urology & Nephrology Center, Mansoura University, Egypt
History Taking (2)History Taking (2)
Associated symptomsAssociated symptoms Fever, chills, other bleeding point, dyspnea, Fever, chills, other bleeding point, dyspnea, recent URI, recent URI,
Painful hematuria:Painful hematuria: stone, inflammation, cancer stone, inflammation, cancer bladder, cancer prostate, SEP, traumabladder, cancer prostate, SEP, trauma
Painless gross hematuriaPainless gross hematuria consider tumorconsider tumor
Urology & Nephrology Center, Mansoura University, Egypt
Evaluation of HematuriaEvaluation of HematuriaPhysical ExaminationPhysical Examination
Evaluation of HematuriaEvaluation of HematuriaPhysical ExaminationPhysical Examination
I- GENERAL EXAMINATION:I- GENERAL EXAMINATION:Growth failureGrowth failureHypertensionHypertensionPallorPallorEdemaEdemaRashRashExamination of the skin for hemorrhagic Examination of the skin for hemorrhagic
spotsspotsAbdomen: search for a mass or tendernessAbdomen: search for a mass or tendernessGeneral manifestations of the causeGeneral manifestations of the cause
Urology & Nephrology Center, Mansoura University, Egypt
LOCAL EXAMINATIONLOCAL EXAMINATION
• External genitalia: bleedingExternal genitalia: bleeding
infectioninfection
traumatrauma
PR examination: prostate or bladder causePR examination: prostate or bladder cause
Suprapubic tenderness or massSuprapubic tenderness or mass
Tender loinTender loin
Palpable renal massPalpable renal masswww.MansFans.com
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
INVESTIGATIONSINVESTIGATIONS
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Study of hemorrhagic profileStudy of hemorrhagic profile
Blood picture:Blood picture:
Sickle cell anemiaSickle cell anemia
LymphomaLymphoma
leukemialeukemia
Urology & Nephrology Center, Mansoura University, Egypt
Urine analysisUrine analysis
Volume:Volume: low in nephritic syndrome low in nephritic syndrome
Colour:Colour: red in macroscopic hematuria, red in macroscopic hematuria, smokey in nephritic syndromesmokey in nephritic syndrome
Bilharzial ovaBilharzial ova
CrystalsCrystals
Malignant cellsMalignant cells
Urology & Nephrology Center, Mansoura University, Egypt
Examination of urine for:
Proteinuria.
Casts.(RBC in nephritic syndrome, PUS
cells in UTI, WBC in pyelonephritis)
Pus.
Bacteria (specific and non specific)
Culture (Ordinary and special)
PCR (TB-DNA)
Urology & Nephrology Center, Mansoura University, Egypt
Ultasound, plain X-ray, I.V.P. (if serum
creatinine is normal), CT, MRI and
possibly angiography, for the diagnosis
of surgical diseases e.g. stone,
malignancy, infection, or
malformations.
Radiological investigationsRadiological investigations
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
Urology & Nephrology Center, Mansoura University, Egypt
RBCs in urine could be examined for its shape to differentiate glomerular (small, distorted) from non glomerular causes (by phase contrast microscopy).
Kidney function tests.
Specific investigations for diagnosis of systemic disease causing haematuria e.g. SLE.
Endoscopic study: to diagnose neoplastic disease , UB ulcers
Kidney biopsy: for glomerular haematuria.
OTHER INVESTIGATIONS
Urology & Nephrology Center, Mansoura University, Egypt
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Yes
Dipstick+Dipstick+ Uriinalysis (UA) with microscopy
RBCs present
•Hemoglobinuria•Myoglobinuria
Appropriate work up and therapy
NO
YesTransient cause?•Sexual intercourse• Infection•GU instrumentation
•Menstruation•Vigorous exerciseYes
Age < 50
Surveillance
Persistent hematuria
Glomerular etiology?•Proteinuria > 500 mg/24 hr•UA shows RBC casts +/- dysmorphic RBCs•Renal insufficiency
NO
Imaging:•Ultrasound •Spiral CT
•Mass•Stricture
•Hydronephrosis
Urology referral
•Cysto+/-•Cytology
•Age > 50•Aromatic amine exposure•smoker
Repeat UA when condition resolved
Nephrology referral
Biopsy
Cystic disease
Nephrology referral
Evaluation of haematuria
Urology & Nephrology Center, Mansoura University, Egypt
Work-up of a child with Work-up of a child with HematuriaHematuria
Work-up of a child with Work-up of a child with HematuriaHematuria
Phase IPhase I:: • Urinalysis ( sediment examination )Urinalysis ( sediment examination )• RBC’s morphologyRBC’s morphology• Urine cultureUrine culture• BUN, Creatinine, Proteins, Electrolytes BUN, Creatinine, Proteins, Electrolytes • Antibodies against strept. & other antigensAntibodies against strept. & other antigens• Complement, ANF, ImmunoglobulinsComplement, ANF, Immunoglobulins• Renal USRenal US• Urinalysis of 1Urinalysis of 1stst degree relatives degree relatives• 24h urine collection: Ca, Creat.,Protein, UA24h urine collection: Ca, Creat.,Protein, UA
Phase IIPhase II:: • Hearing testHearing test• CystoscopyCystoscopy• Renal biopsyRenal biopsy
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Isolated hematuriaIsolated hematuriaIsolated hematuriaIsolated hematuria
The child needs to be monitored for the The child needs to be monitored for the appearance of new clinical signs:appearance of new clinical signs:
hypertensionhypertension proteinuriaproteinuria changes in the pattern or severity of hematuriachanges in the pattern or severity of hematuria
If there is no change in the first year,observation If there is no change in the first year,observation at at yearlyyearly intervals is adequate intervals is adequate
Urology & Nephrology Center, Mansoura University, Egypt
Isolated hematuriaIsolated hematuria Possible Possible outcomeoutcome
Isolated hematuriaIsolated hematuria Possible Possible outcomeoutcome
Disappearance of hematuriaDisappearance of hematuria
Hematuria will persist -Hematuria will persist -
follow-up should be continuedfollow-up should be continued
The hematuria will no longer be The hematuria will no longer be “isolated” - further investigation“isolated” - further investigation
Urology & Nephrology Center, Mansoura University, Egypt
Most common causes of hematuria by age and Most common causes of hematuria by age and sexsex
Age/sex Age/sex Common causesCommon causes0-20 AGN, UTI, 0-20 AGN, UTI,
congenital urinary tract congenital urinary tract anomalies with obstructionanomalies with obstruction
20-40 male UTI, stones, bladder tumor20-40 male UTI, stones, bladder tumor40-60 female bladder tumor, stone, UTI40-60 female bladder tumor, stone, UTI>60 male BPH, bladder tumor, UTI>60 male BPH, bladder tumor, UTI>60 woman Bladder tumor, UTI>60 woman Bladder tumor, UTI
Urology & Nephrology Center, Mansoura University, Egypt
1. Treatment of the cause.
2. Haemostatic e.g.: Cyclokapron. Vitamin K DDAVP Frish frozen plasma.
3. Haematenics and blood transfusion.
Treatment Of Haematuria