History

Fact Explanation
Introduction This Haemolytic uremic syndrome is characterized by triad of acute progressive renal failure, microangiopathic haemolytic anaemia and thrombocytopenia. Typically this is followed by a diarrhoeal illness. This is identified as the most common cause of acute renal failure in paediatric population[2][8].
Features of gastroenteritis for few days Typically this condition is occur secondary to gasrointestinal infection ( eg; E Coli 0157, Shigella infection) . Patient will give a history of blood stained diarrhoea, fever, abdominal pain for few days duration[1][2].
Features of acute renal failure The toxins from invasive gastrointestinal infection enters through bowel mucosa and enters endothelial cells of the kidney causing intravascular thrombosis. This leads to renal failure. Reduced urine output, uraemia( nausea, vomiting, confusion), hyperkalemia( body weakness, arrest) and metabolic acidosis can be seen in these patients. This is occur in 97% of patients[3].
Features suggestive of arterial and microvascular thrombi formation With the toxins localized in other organs also can induce clotting cascade leading to arterial and microvascular thrombi formation. These presentations are not much common[4]. Brain can affect giving symptoms of confusion/ drowsiness, development of seizures, paralysis, paresthesias. patient may present with trensient ischemic attacks or strokes[5]. Patient will present with a history of chest pain, palpitation, shortness of breath in cardiac involvement as microvascular ischemia can affect cardiac function causing problems with conduction defects and can ultimately leads to cardiac failure[6].
History of suggestive of increased bleeding tendency Following thrombi formation there is an excessive consumption of platelets, finally leading to thrombocytopenia. So patient may present with increased tendency of bleeding. there will be multiple bruises on the skin/mucous membranes, groups of pinpoint-sized dots on the skin and bleeding from mucus membranes like gum bleeding, nasal bleeding, per rectal bleeding, menorrhagia and haematuria[7].
Easy fatigue, shortness of breath, tiredness Microangiopathic hemolytic anemia which is a caused by red blood cell destruction with mechanical injury while passing through occluded blood vessels . This causes fragmentation of red blood cells and hemolysis giving features of anaemia[3].
Yellowish discoloration of eyes With excessive destruction of red blood cells there will be excess bilirubin production causing jaundice[8].
history of any suspected factors precipitating the disease Drug induced Haemolytic-uremic syndrome[9] can occur following use of some Anticancer agents(eg; cisplatin), immunotherapeutic agents(eg;cyclosporine), antiplatelet agents(eg; clopidogrel), antiviral drugs( eg; Valacyclovir) and quinine. Oral contraceptive pills reported to cause this condition. Some vaccines[10] are known to precipitate the disease like influenza triple-antigen vaccine, typhoid-paratyphoid A and B (TAB) vaccine and polio vaccine.
Past medical history Past medical history also very important as some disease conditions are known to precipitate Haemolytic-uremic syndrome[16]. Eg:1) Posttransplantation hemolytic-uremic syndrome can occur following kidney/ bone marrow transplantation[11] 2) Primary glomerulopathies[12] 3) Collagen-vascular disorders like SLE and antiphospholipid antibody syndrome[13] 4) hypertention causing malignant hypertension[14] 5) Some cancers like mucin-producing adenocarcinoma[9] 6) some bacerial infections with E coli, Salmonella, Campylobacter jejuni, Neisseria meningitidis, Streptococcus pneumoniae, Legionella pneumophila[15] 7) Some viral infections caused by Human immunodeficiency virus (HIV), Influenza virus, Epstein-Barr virus and Herpes simplex virus[15]
Obstetric history Pregnancy( due to increase procoagulant factors and decrease fibrinolytics) and post partum period is at risk of developing Haemolytic-uremic syndrome[16].
Family history There is a link with genetic mutations. So family history of symptoms( mentioned above) suggestive of Haemolytic-uremic syndrome is important[16].
References
  1. TSCHAPE H, PRAGER R, STRECKEL W, FRUTH A, TIETZE E, BöHME G. Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source. Epidemiol Infect [online] 1995 Jun, 114(3):441-450 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271295
  2. MCLAINE PN. Hemolytic uremic syndrome: Events of the past decade Paediatr Child Health [online] 2002 Oct, 7(8):533-537 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798609
  3. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  4. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913
  5. SCHLIEPER A, ORRBINE E, WELLS G, CLULOW M, MCLAINE P, ROWE P. Neuropsychological sequelae of haemolytic uraemic syndrome Arch Dis Child [online] 1999 Mar, 80(3):214-220 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717871
  6. NORIS M, BRESIN E, MELE C, REMUZZI G, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Atypical Hemolytic-Uremic Syndrome [online] 1993 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301541
  7. LOIRAT C, FRéMEAUX-BACCHI V. Atypical hemolytic uremic syndrome Orphanet J Rare Dis [online] :60 [viewed 23 September 2014] Available from: doi:10.1186/1750-1172-6-60
  8. JEFFREY G, KIBBLER CC, BAILLOD R, FARRINGTON K, MORGAN MY. Cholestatic jaundice in the haemolytic-uraemic syndrome: a case report. Gut [online] 1985 Mar, 26(3):315-319 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1432642
  9. LAKSHMINARAYANA G, RAJESH R, JOJO A, KURIAN G, UNNI VN. Recurrent hemolytic uremic syndrome Indian J Nephrol [online] 2008 Jul, 18(3):127-129 [viewed 23 September 2014] Available from: doi:10.4103/0971-4065.43694
  10. AVCı Z, BAYRAM C, MALBORA B. Hepatitis B Vaccine-Associated Atypical Hemolytic Uremic Syndrome Turk J Haematol [online] 2013 Dec, 30(4):418-419 [viewed 23 September 2014] Available from: doi:10.4274/Tjh-2013.0226
  11. JOSEPH C, GATTINENI J. Complement disorders and hemolytic uremic syndrome Curr Opin Pediatr [online] 2013 Apr, 25(2):209-215 [viewed 23 September 2014] Available from: doi:10.1097/MOP.0b013e32835df48a
  12. JANSSEN VAN DOORN K, DIRINCK E, VERPOOTEN GA, COUTTENYE MM. Complement factor H mutation associated with membranoproliferative glomerulonephritis with transformation to atypical haemolytic uraemic syndrome Clin Kidney J [online] 2013 Apr, 6(2):216-219 [viewed 23 September 2014] Available from: doi:10.1093/ckj/sfs190
  13. SALVADORI M, BERTONI E. Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations World J Nephrol [online] 2013 Aug 6, 2(3):56-76 [viewed 23 September 2014] Available from: doi:10.5527/wjn.v2.i3.56
  14. LEE HW, CHUNG MJ, KANG H, CHOI H, CHOI YJ, LEE KJ, LEE SW, HAN SH, KIM JS, SONG SY. Gemcitabine-Induced Hemolytic Uremic Syndrome in Pancreatic Cancer: A Case Report and Review of the Literature Gut Liver [online] 2014 Jan, 8(1):109-112 [viewed 23 September 2014] Available from: doi:10.5009/gnl.2014.8.1.109
  15. MOSSORO C, GLAZIOU P, YASSIBANDA S, LAN NT, BEKONDI C, MINSSART P, BERNIER C, LE BOUGUéNEC C, GERMANI Y. Chronic Diarrhea, Hemorrhagic Colitis, and Hemolytic-Uremic Syndrome Associated with HEp-2 Adherent Escherichia coli in Adults Infected with Human Immunodeficiency Virus in Bangui, Central African Republic J Clin Microbiol [online] 2002 Aug, 40(8):3086-3088 [viewed 23 September 2014] Available from: doi:10.1128/JCM.40.8.3086-3088.2002
  16. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913

Examination

Fact Explanation
Pallor This condition is associated with microangiopathic hemolytic anemia causing red blood cell destruction giving signs of anaemia. Due to the mechanical injury with high shear stress created by microvascular thrombosis is believed to cause fragmentation of red blood cells and hemolysis[1].
Jaundice This is due to the excessive destruction of red blood cells with microangiopathic haemolytic anaemia[4].
Hypertension These patients will have increased blood pressure due to renal involvement[2].
Anuria/ oliguria Patient will have either no urine out put or reduced urine out put with acute renal failure[1].
Oedema Due to acute renal failure there will be fluid retention causing generalized body oedema[1][5].
Neurologic examination Neurologic examination reveals alteration in mental status( confusion/ drowsiness), development of seizures, hemiplegia, paresthesias and cranial nerve palsy. With focal and segmental distribution of microthrombi, these neurological manifestations can be seen[3].
Cardiovascular examination Cardiovascular examination will reveals dyspnoic patient, irregular pulse and features of cardiac failure like ankle oedema, gallop rhythm. The presence of systemic microvascular ischemia in these patients can affect cardiac fuction causing conduction defects and these leads finally to cardiac failure[6].
Signs of increase bleeding tendency There will be multiple purpura/ ecchymotic patches and groups of petechiaeand evidence of gum/ nasal bleeding of bleeding from other mucus membranes as clotting in small blood vessels of the body causing reduction in platelet count (thrombocytopenia)[7].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913
  3. SCHLIEPER A, ORRBINE E, WELLS G, CLULOW M, MCLAINE P, ROWE P. Neuropsychological sequelae of haemolytic uraemic syndrome Arch Dis Child [online] 1999 Mar, 80(3):214-220 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717871
  4. JEFFREY G, KIBBLER CC, BAILLOD R, FARRINGTON K, MORGAN MY. Cholestatic jaundice in the haemolytic-uraemic syndrome: a case report. Gut [online] 1985 Mar, 26(3):315-319 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1432642
  5. LAKSHMINARAYANA G, RAJESH R, JOJO A, KURIAN G, UNNI VN. Recurrent hemolytic uremic syndrome Indian J Nephrol [online] 2008 Jul, 18(3):127-129 [viewed 23 September 2014] Available from: doi:10.4103/0971-4065.43694
  6. NORIS M, BRESIN E, MELE C, REMUZZI G, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Atypical Hemolytic-Uremic Syndrome [online] 1993 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301541
  7. LOIRAT C, FRéMEAUX-BACCHI V. Atypical hemolytic uremic syndrome Orphanet J Rare Dis [online] :60 [viewed 23 September 2014] Available from: doi:10.1186/1750-1172-6-60

Differential Diagnoses

Fact Explanation
Thrombotic thrombocytopenic purpura Thrombotic Thrombocytopenic Purpura is a haematological disorder. It is characterized by thrombus formation in small blood vessels of the body. As thrombus consume platelets in the blood it causes reduction in platelet count (thrombocytopenia). So there ia a bleeding tendency associated with this disease[1]. In Haemolytic uremic syndrome thrombus formation mainly affect renal circulation causing progressive acute renal failure while Thrombotic Thrombocytopenic Purpura mainly affect cerebral circulation causing cerebral infarctions[7].
Disseminated Intravascular Coagulation In Disseminated intravascular coagulation there is generalized activation of blood clotting leading to systemic thrombus formation. These microvascular thrombi in all over the body will leads to multiple organ failure. Following this excessive consumption of coagulation factors and platelets there will be lack of clotting ability in circulation causing severe bleeding[2]. In Haemolytic uremic syndrome it mainly affect kidneys and there will be only thrombocytopenia with normal levels of clotting factors[7].
Hypertensive emergency In a hypertensive emergency there is elevated blood pressure more than normal value resulting in end organ damage. In this condition central nervous system, cardiovascular system and renal system are commonly involved[3]. Haemolytic uraemic syndrome mainly affect renal system and can rarely affect cardiovascular and central nervous systems. There will be low haemoglobin and platelet counts in Haemolytic uraemic syndrome and counts will be normal in hypertension[8].
Immune Thrombocytopenic Purpura In immune thrombocytopenic purpura there is a immune mediated reduction in circulating platelets which manifests as increase bleeding tendency[4]. Similer to haemolytic uraemic syndrome it also can manifest as easy bruising or petechiae with bleeding tendency. But it will have prominent features of acute renal failure[7].
Stroke Sudden onset neurologic manifestations such as alteration in mental status like confusion and drowsiness, seizures, muscle paralysis, paresthesias, visual problems and other cranial nerve involvement is associated with strokes[5]. Microthrombi formation with haemolytic uraemic syndrome will give symptoms gradually and seizure are more prominent among symptoms[6].
Pre eclampsia In a pregnancy pre eclampsia is a differential diagnosis. Pre eclampsia cause haemolysis, elivated liver enzymes, thrombocytopenia with protein urea and hypertensison. This need to be differentiate from haemolytic uraemic syndrome. Haemolytic uraemic syndrome will not be associated with elevated liver enzymes. Pre eclampsia will resolve with the delivery of the patient[9].
References
  1. TSAI HM. Pathophysiology of thrombotic thrombocytopenic purpura Int J Hematol [online] 2010 Jan, 91(1):1-19 [viewed 10 September 2014] Available from: doi:10.1007/s12185-009-0476-1
  2. SCHIEFER B, SEARCY G. Disseminated intravascular coagulation and consumption coagulopathy. Can Vet J [online] 1975 Jun, 16(6):151-159 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1696929
  3. HICKLER RB. "Hypertensive emergency": a useful diagnostic category. Am J Public Health [online] 1988 Jun, 78(6):623-624 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1350270
  4. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 10 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  5. NICOL MB, THRIFT AG. Knowledge of Risk Factors and Warning Signs of Stroke Vasc Health Risk Manag [online] 2005 Jun, 1(2):137-147 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993942
  6. SCHLIEPER A, ORRBINE E, WELLS G, CLULOW M, MCLAINE P, ROWE P. Neuropsychological sequelae of haemolytic uraemic syndrome Arch Dis Child [online] 1999 Mar, 80(3):214-220 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717871
  7. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  8. SERKE S, RIESS H, OETTLE H, HUHN D. Elevated reticulocyte count - a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report Br J Cancer [online] 1999 Mar, 79(9-10):1519-1521 [viewed 23 September 2014] Available from: doi:10.1038/sj.bjc.6690242
  9. DIXIT S, TIWARI AK, PANDEY PK, RAINA V. Successful outcome of therapeutic plasma exchange in post-partum haemolytic-uraemic syndrome: a case report Blood Transfus [online] 2012 Oct, 10(4):533-535 [viewed 23 September 2014] Available from: doi:10.2450/2012.0158-11

Investigations - for Diagnosis

Fact Explanation
Full blood count This condition is associated with thrombocytopenia and anaemia causing reduced haemoglobin level. If there is any ongoing gastrointestinal infection there will be increase in WBC count as well[4].
Renal function tests like serum creatinine, blood urea and Urine full report As renal involvement is common in these patients, Urine full report will reveals presence of blood protein and red blood cell casts. Serum creatinine levels and blood urea levels will be elevated[1].
Serum electrolytes There will be hyperkalaemia and hyperphosphataemia[5].
Peripheral blood film examination A peripheral blood smear examination will reveals thrombocytopenia and red cell fragmentation(schistocytes) as prominent features[6].
Arterial Blood Gas analysis Patients with acute renal failure may develop metabolic acidosis[7].
PT/INR, APTT As there is no clotting factor defect these tests are normal and helps in differentiating this bleeding tendency with other clotting disorders[8].
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning /MRI useful in the medical history or physical findings suggestive of central nervous system involvement[2].
ECG, Echocardiogram In the presence of cardiovascular involvement these tests are useful[3].
Lactic dehydrogenase (LDH) levels may be elevated with the red blood cell dystruction[9].
Haptoglobin levels In this condition Haptoglobin levels can be decreased[9].
Stool culture This will be useful in the presence of gastroenteritis to identify the causative organism[10].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. SCHLIEPER A, ORRBINE E, WELLS G, CLULOW M, MCLAINE P, ROWE P. Neuropsychological sequelae of haemolytic uraemic syndrome Arch Dis Child [online] 1999 Mar, 80(3):214-220 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717871
  3. NORIS M, BRESIN E, MELE C, REMUZZI G, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Atypical Hemolytic-Uremic Syndrome [online] 1993 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301541
  4. VALAVI E, ANSARI MJ. Hemolytic uremic syndrome following Hemiscorpius lepturus (scorpion) sting Indian J Nephrol [online] 2008 Oct, 18(4):166-168 [viewed 23 September 2014] Available from: doi:10.4103/0971-4065.45293
  5. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913
  6. KOK VC, WU SC, LEE CK. Successful Remission of Hemolytic-Uremic Syndrome During the Third-line Weekly Gemcitabine for Metastatic Breast Cancer Breast Cancer (Auckl) [online] :57-59 [viewed 23 September 2014] Available from: doi:10.4137/BCBCR.S14920
  7. POULSEN VO, NIELSEN J, POULSEN TD. Rapidly Developing Toxic Epidermal Necrolysis Case Rep Emerg Med [online] 2013:985951 [viewed 23 September 2014] Available from: doi:10.1155/2013/985951
  8. KESHTKAR-JAHROMI M, MOHEBTASH M. Hemolytic uremic syndrome and Clostridium difficile colitis J Community Hosp Intern Med Perspect [online] , 2(3):10.3402/jchimp.v2i3.19064 [viewed 23 September 2014] Available from: doi:10.3402/jchimp.v2i3.19064
  9. KOK VC, WU SC, LEE CK. Successful Remission of Hemolytic-Uremic Syndrome During the Third-line Weekly Gemcitabine for Metastatic Breast Cancer Breast Cancer (Auckl) [online] :57-59 [viewed 23 September 2014] Available from: doi:10.4137/BCBCR.S14920
  10. OLSEN SJ, MILLER G, BREUER T, KENNEDY M, HIGGINS C, WALFORD J, MCKEE G, FOX K, BIBB W, MEAD P. A Waterborne Outbreak of Escherichia coli O157:H7 Infections and Hemolytic Uremic Syndrome: Implications for Rural Water Systems Emerg Infect Dis [online] 2002 Apr, 8(4):370-375 [viewed 23 September 2014] Available from: doi:10.3201/eid0804.000218

Investigations - Fitness for Management

Fact Explanation
Renal function tests- UFR, serum creatinine, blood urea and serum electrolytes This is useful in assessing the progression/ improvement of acute renal failure during the management[1].
Full Blood Count Assess the degree of thrombocytopenia and anaemia will helpful in deciding the patients present condition[1][4].
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in assessing central nervous system involvement[2].
Serum troponin levels echocardiogram, electrocardiogram The presence of systemic microvascular ischemia in these patients can affect cardiac fuction causing conduction defects and congestive cardiac failure. In these patient serum troponin levels in clinical suspected myocardial infarction and ECG, echocardiogram also very important in assessing the cardiac status[3].
Blood grouping and cross matching This is useful in management if the transfusion is needed following severe[5].
Arterial blood gas analysis This is also useful in assessing the fitness in the presence of metabolic acidosis[6].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. SCHLIEPER A, ORRBINE E, WELLS G, CLULOW M, MCLAINE P, ROWE P. Neuropsychological sequelae of haemolytic uraemic syndrome Arch Dis Child [online] 1999 Mar, 80(3):214-220 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717871
  3. NORIS M, BRESIN E, MELE C, REMUZZI G, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Atypical Hemolytic-Uremic Syndrome [online] 1993 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301541
  4. VALAVI E, ANSARI MJ. Hemolytic uremic syndrome following Hemiscorpius lepturus (scorpion) sting Indian J Nephrol [online] 2008 Oct, 18(4):166-168 [viewed 23 September 2014] Available from: doi:10.4103/0971-4065.45293
  5. MAKROO R, GUPTA R, BHATIA A, ROSAMMA NL. Rh phenotype, allele and haplotype frequencies among 51,857 blood donors in North India Blood Transfus [online] 2014 Jan, 12(1):36-39 [viewed 23 September 2014] Available from: doi:10.2450/2013.0300-12
  6. LEE YC, WANG JS, SHIANG JC, TSAI MK, DENG KT, CHANG MY, WANG HH, HO LC, CHEN YT, HUNG SY. Haemolytic uremic syndrome following fire ant bites BMC Nephrol [online] :5 [viewed 23 September 2014] Available from: doi:10.1186/1471-2369-15-5

Investigations - Followup

Fact Explanation
Renal function tests- UFR, serum creatinine, blood urea and serum electrolytes These tests are useful in follow up to see the renal status as some patients can progress into chronic renal failure[1].
Full Blood Count and reticulocyte count These are useful in followup as well to see the patients current condition[2].
Ultrasound scan of the abdomen and pelvis This will be useful to exclude any other pathology causing renal failure( obstruction) or to exclude any associated renal complications like hydronephrosis[1].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. VALAVI E, ANSARI MJ. Hemolytic uremic syndrome following Hemiscorpius lepturus (scorpion) sting Indian J Nephrol [online] 2008 Oct, 18(4):166-168 [viewed 23 September 2014] Available from: doi:10.4103/0971-4065.45293

Investigations - Screening/Staging

Fact Explanation
Renal biopsy This is useful in identifying the primary cause for acute renal failure in the absent of clear symptoms. But this is not usually done in Haemolytic-uremic syndrome. If done there will be frequent arterial thrombotic microangiopathic lesions. In some cases there will be glomerular thrombotic microangiopathic lesions and cortical necrosis. Prognosis will be poor with the second type[1].
Genetic screening with karyotyping Genetic screening of high risk patients will be helpful[2].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913

Management - General Measures

Fact Explanation
Fluid and electrolyte balance Patient can develop hyperkalaemia and hyperphosphataemia. So close monitoring and immediate treatments will be necessary in the presence of severe electrolyte imbalance[1][3].
Adequate blood-pressure control Patients can develop hypertension especially progressed in to chronic renal failure. So close monitoring and treatment with anti hypertensives will be needed. Angiotensin-converting enzyme inhibitors/ angiotensin-receptor blockers will be useful[2].
Optimize nutritional requirement In an acute stage of the illness nutritional support is very important with balanced diet. Protein restriction will be needed in patients progressed into the chronic renal failure. If the patient is having severe diarrhea parenteral nutrition may be indicated[3].
Good hygienic practices This is very important in preventing food/ water bone diseases like E Coli, Salmonella infections which can precipitate the disease. This is important in individual level as well as in community level in preventing[4].
Blood transfusion This is indicated in severe symptomatic anaemia with haemoglobin level less than 5-7 g/dl[2].
Platelet infusion elet infusion is consider in presence of active bleeding or in preparing for a surgery[2].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913
  3. GRISARU S. Management of hemolytic-uremic syndrome in children Int J Nephrol Renovasc Dis [online] :231-239 [viewed 23 September 2014] Available from: doi:10.2147/IJNRD.S41837
  4. THOMAS DE, ELLIOTT EJ. Interventions for preventing diarrhea-associated hemolytic uremic syndrome: systematic review BMC Public Health [online] :799 [viewed 23 September 2014] Available from: doi:10.1186/1471-2458-13-799

Management - Specific Treatments

Fact Explanation
Management of acute renal failure In the early stage close monitoring of the renal function with controlling fluid balance, maintaining electrolyte balance and hypertension will be enough. If the renal function is severely affected of if the patient is having uremic symptoms haemodialysis will be helpful. If patient go into end stage renal failure kidney transplantation will be the treatment option[1][3].
Multidisciplinary team management with nephrologist, haematologist, neurologist and intensive care unit team. Nephrologist management is very important as 97% of patients are at risk of going into acute renal failure[1]. Haematologist's managemet will be needed in the present of anaemia and thrombocytopenia following microvasculat thrombi formation. Neurologist management need in cases of neurological involvement[4] and cardiuologist management will be needed in cardiac involvement[5]. As close monitoring is needed in acute stage, ICU care will also very important[7]. In a complicated state patient should be transfer in to a tertiary care hospital will specialized treatment available.
Antibiotic treatment This will be useful if the patient go into septicemia following gastroenteritis. Stool culture will support to select the antibiotic[6].
Plasma exchange This is useful as initial therapy to remove toxins from the circulation. This will be most helpful in complicated situations like renal/ cardiac failure[2][3].
Anti platelet agents These drugs like aspirin inhibit the cyclo oxygenase system by reducing the thromboxane A2 levels which is potent platelet activator. From this mechanism anti platelet agents reduce thrombi formation and from that it minimize the development of thrombocytopenia[8].
Plasma infusion This is another method of treatment Plasma infusion need to be started within 24 hours of the presentation and should continue once or twice a day for a least of 2 days following resolution. Steroids and immunosuppressive drugs will help in preventing antibody formation after plasma discontinuation[3].
Seizure management As patient are at risk of seizure development, prophylactic phenytoin can be give to patients with neurological symptoms[9].
Monoclonal antibody (anti-C5a) therapy and soluble complement inhibitors These group of new drugs prevent compliment mediated damage by preventing compliment activation[3].
Gene therapy This is another effective newer treatment option[3].
Splenectomy This has a limited place in treating the disease other than in plasma-resistant and relapsing cases[3].
Prophylactic fresh frozen plasma Exchange and infusion of fresh frozen plasma is known to maintain native and allograft kidney function by both treating and preventing recurrent episodes of the disease[3].
References
  1. DE CHADARéVIAN JP, GOODYER PR, KAPLAN BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J [online] 1980 Sep 6, 123(5):391-394 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704806
  2. DIXIT S, TIWARI AK, PANDEY PK, RAINA V. Successful outcome of therapeutic plasma exchange in post-partum haemolytic-uraemic syndrome: a case report Blood Transfus [online] 2012 Oct, 10(4):533-535 [viewed 23 September 2014] Available from: doi:10.2450/2012.0158-11
  3. NICKAVAR A, SOTOUDEH K. Assesment, Treatment and Prevention of Atypical Hemolytic Uremic Syndrome Int J Prev Med [online] 2013 Jan, 4(1):6-14 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570913
  4. SCHLIEPER A, ORRBINE E, WELLS G, CLULOW M, MCLAINE P, ROWE P. Neuropsychological sequelae of haemolytic uraemic syndrome Arch Dis Child [online] 1999 Mar, 80(3):214-220 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717871
  5. NORIS M, BRESIN E, MELE C, REMUZZI G, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Atypical Hemolytic-Uremic Syndrome [online] 1993 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301541
  6. GRISARU S. Management of hemolytic-uremic syndrome in children Int J Nephrol Renovasc Dis [online] :231-239 [viewed 23 September 2014] Available from: doi:10.2147/IJNRD.S41837
  7. DE SOUZA RL, ABREU CARVALHAES JT, SANAE NISHIMURA L, DE ANDRADE MC, CABILIO GUTH BE. Hemolytic Uremic Syndrome in Pediatric Intensive Care Units in S?o Paulo, Brazil Open Microbiol J [online] :76-82 [viewed 23 September 2014] Available from: doi:10.2174/1874285801105010076
  8. KOK VC, WU SC, LEE CK. Successful Remission of Hemolytic-Uremic Syndrome During the Third-line Weekly Gemcitabine for Metastatic Breast Cancer Breast Cancer (Auckl) [online] :57-59 [viewed 23 September 2014] Available from: doi:10.4137/BCBCR.S14920
  9. BONETTI V, MANGIA CM, ZUZA JM, BARCELOS MO, FONSECA MM, NERY SP, CARVALHAES JT, ANDRADE MC. Hemolytic-Uremic Syndrome in Uberl?ndia, MG, Brazil ISRN Pediatr [online] 2011:651749 [viewed 23 September 2014] Available from: doi:10.5402/2011/651749