FROM NELSON LATEST ARTICLES AND ISPN GUIDELINES DR SIDDHARTHA JOSHI DR JOSHI SIDDHARTHA

1. HAEMOLYTIC UREMIC SYNDROME
DR SIDDHARTHA JOSHI
MBBS,D.PAEDIATRICS(SETH
GSMC medical college)
DNB paediatrics (delhi)

2. INTRODUCTION
• ITS UNCOMMON DISEASE WITH INCIDENCE
OF 3-8/100000 POPULATION PER YEAR BUT
HUS IS A ONE OF THE COMMON CAUSE OF
COMMUNITY ACQUIRED ACUTE KIDNEY
INJURY IN YOUNG CHILDREN.
• ITS MOST COMMON FORM OF THROMBOTIC
MICROANGIOPATHY IN CHILDREN.
• ITS MOST COMMON CAUSE OF CHILDHOOD
AKI REQUIRING DIALYSIS.

3. WHAT IS HAEMOLYTIC UREMIC
SYNDROME
• MICROANGIOPATHIC HAEMOLYTIC
ANAEMIA(HB <10%,HAEMATOCRIT
<30%,FRAGMENTED RBC >2% WITH EITHER
LDH >450 IU/L OR UNDETECTABLE
HAPTOGLOBIN <30 MG/DL
• THROMBOCYTOPENIA(<1,50,000)
• ACUTE RENAL FAILRE(UREMIA) INCREASE IN
SERUM CREATININE LEVEL BY 50% OF
BASELINE

4. ETIOLOGY
• THE MOST COMMON FORM OF HUS IS CAUSED BY
SHIGA TOXIN PRODUCING E.COLI WHICH CAUSES
PRODROMAL ACUTE ENTERITIS AND IS COMMONLY
TERMED STEC-HUS OR DIARRHOEA ASSOCIATED HUS.
• IN THE SUBCONTINENT OF ASIA AND IN SOUTHERN
AFRICA THE TOXIN OF SHIGELLA DYSENTERIAE TYPE 1
IS CAUSATIVE WHEREAS IN WESTERN COUNTRIES
VEROTOXIN OR SHIGA TOXIN PRODUCING E.COLI IS
THE USUAL CAUSE.
• STEC-HUS ACCOUNT FOR 90% OF ALL CHILDHOOD
• THE RESERVIOR FOR STEC IS THE INTESTINAL TRACT
OF DOMESTIC ANIMAL AND USUALLY COWS.

5. • DISEASE COMMONLY
TRANSMITTED BY UNDERCOOKED MEAT
OR UNPASTEURISED MILK AND APPLE CIDER .
• LOCAL OUT BREAKS HAVE
FOLLOWED THE INGETION
OF UNDERCOOKED
CONTAMINATED
HAMBURGER OR OTHER FOOD
CROSS CONTAMINATED ON
UNWASHED CUTTING BOARDES
AT FAST FOOD RESTAURANTS
AND CONTAMINATED
MUNICIPAL WATER SUPPLIES,
PETTING FARM,SWIMMING IN
CONTAMINATED POND POOL OR
LAKES,CONTAMINATED LETTUCE RAW
SPINACH AND BEAN SPROUTS
VERY RARELY PERSON TO PERSON
TRANSMISSION ALSO OCCUR
A MAJOR FEATURE OF GENETIC FORM OF
HUS IS THE ABSCENCE OF PRECEDING
DIARRHOEAL PRODROME.
• GENETIC FORM OF HUS CAN BE INDOLENT AND UNREMITTING ,ONCE THEY BECOME MANIFEST
THEY CAN BE RELAPSING PATTERN PRECIPITATED BY AN INFECTIOUS ILLNESS.THE LETTER FEATURE
EXPLAIN THE ASSOCIATION OF MANY INFECTION WITH HUS PARTICULARLY ,REPORT PUBLISHED
BEFORE RECOGNISING PATHOPHYSIOLOGY OF STEC HUS AND NEURAMINIDASE PRODUCING
PNEOMOCOCCI PRODUCING HUS

6. ETIOLOGICAL CLASSIFICATION
• DIARRHOEA ASSOCIATED HUS (D+) (TYPICAL)
• STEC(O157:H7)
• STEC(E.COLI 0121,ECOLI 0104:H4)
• NON STEC (SHIGELLA DYSENTERIAE TYPE 1)
• CITROBACTER,CAMPHLOBACTOR
• HUS SECONDARY TO SYSTEMIC INFECTION (D-)
• NEURAMINIDASE(STREPTOCOCCUS PNEUMONIA)
• HIV
• INFLUENZA
• EPSTEIN BARR VIRUS
• HHV 6
• PARVOVIRUS B19
• MALARIA
• DENGUE
• RICKETTSIA
• SALMONELLA TYPHI
• BARTONELLA
• LEPTOSPIRA

7. • ATYPICAL HUS DUE TO COMPLEMENT DYSREGULATION (D-)
• FACTOR H DEFICIENCY
• FACTOR I DEFICIENCY
• FACTOR B DEFICIENCY
• MEMBRANE COFACTOR DEFICIENCY CD46
• C3 DEFICIENCY
• THROMBOMODULIN DEFICIENCY
• ANTI COMPLEMENT FACTOR H ANTIBODY
• UNKNOWN
• THROMBOTIC THROMBOCYTOPENIC PURPURA
• INHERITED ADAMTS13 DEFICIENCY
• ACQUIRED ADAMTS 13 DEFICIENCY
• PREGNANCY ASSOCIATED
• VITAMIN B12 DEFICIENCY
• DEFECTIVE COBALAMINE METABOLISM DUE TO HOMOZYGOS OR COMPUND
HETEROZYGOUS MUTATION IN MMACHC

8. • DRUG INDUCED
• CYCLOSPORIN
• TACROLIMUS
• MITHRAMYCIN
• QUININE
• COCAINE
• ANTIVASCULAR ENDOTHELIAL GROWTHFACTOR THERAPY
• SYSTEMIC DISEASE ASSOCIATED
• SYSTEMIC LUPUS ERYTHEMATOUS
• COEXISTING NEPHROPATHY
• MALIGNANT HYPERTENSION
• COBALAMIN C DEFECT
• DIACYLGLYCEROL KINASE EPSIOLN MUTATION
• TRANSPLANT ASSOCIATED
• STEM CELL TRANSPLANT
• BONEMARROW TRANSPLANT
• RENAL,HEART,INTESTINE

9. PATHOGENESIS
• SHIGA TOXIN OR HIGHLY HOMOLOGUS SHIGA LIKE
VEROTOXIN INDUCED HUS TOXIN EASILY
ABSORBED FROM
COLONIC MUCOSA
TOXIN BIND TO ENDOTHELIAL CELL
OF GLOMERULUS PREDOMINANTLY
PROXIMAL RENAL TUNBULE AND
OTHER ORGAN AND ALTERATION IN
HOMEOSTASIS
TOXIN DIRECTLY
PRAMOTE
PLATELET TO
PRAMOTE
AGGREGATION
MECHANICAL
INJURY TO
RBC
NONIMMUNE
HEMOLYTIC
ANEMIA
WITH DCT
NEGATIVE

10. • PNEUMOCOCCAL ASSOCIATED HUS
PNEURAMINIDASE CLEAVES
SIALIC ACID ON
ENDOTHELIAL
CELLS,PLATELETS AND RBC
EXPOSED UNDERLYING
CRYPTIC FRIEDENREICH
ANTIGEN
ENDOGENEOUS IGM
ANTIBODY RECOGNISE T
ANTIGEN AND REACT WITH
THEM
TRIGGER HAEMOLYSIS
POSITIVE
DCT

11. ADAMTS 13 DEFICIENCY

13. NORMAL COMPLEMENT CASCADE

14. ABNORMAL
DEFICIENT
FACTOR
FUNCTION %AHUS MINIMUM AGE ESRD %
C3 KEY ROLE IN COMPLEMENT
CASCADE,SUBSTRATE FOR
C3 CONVERTASE,ACTIVE
FORM C3B REQUIRED FOR
ENZYMATIC COMPLXES
2-10 >1 YEAR 60
COMPLEMENT
FACTOR H
BIND C3B AS COFACTOR
TO INACTIVE IC3B
20-30 <1 MONTH 50-70
FACTOR I SERINE PROTEASES
REQUIRES A COFACTOR
TO CLEAVE C3B OR C4B
4-10 <1 MONTH 50
MEMBRANE CO
FACTOR PROTEIN
CD46
BIND C3B AND C4B
COFACTOR ACTIVITY
5-15 >12 MONTH 0-10
FACTOR B PROVIDE CATALYTIC SITE
FOR THE C3 CONVERTASE
1-4 <12 MONTH 50
ANTI FACTOR H
ANTIBODY
BIND TO FH TO REDUCE
CELL SURFACE
COMPLEMENT
REGULATORY ACTIVITY
6-25 5-15YEAR 30-40
THROMBOMODU
LIN
ACCELERATE FIMEDIATED
INACTIVATION OF C3B IN
PRESENCE OF COFACTORS
3-5 1 MONTH 50
DIACYL GLYCEROL
KINASE E
CAUSE PROTHROMBOTIC
STATE
25-30 <12 MONTH 80-100

15. CLINICAL FEATURE AND
PRESENTATION
• HUS FOLLOWING SHIGELLOSIS ,THE DYSENTERY IS USUALLY PERSISTENT AND MAY
CONTINUE BEYOND THE DEVELOPMENT OF HUS.GENERALLY HUS PRESENT WITHIN 5-7 DAYS
AFTER THE ONSET OF DIARRHOEA AND MAY PRESENT AFTER 4 WEEK OF ONSET AS WELL.
• IN THOSE NOT RELATED TO SHIGELLOSIS,PRODROME OF DIARRHOEA WHICH IS MILD OR
SEVERE OFTEN BLOODY AND MAY SUBSIDE BY DEVELOPMENT OF HUS
• HUS CAN PRESENT WITH EITHER SIGNIFICANT DEHYDRATION OR VOLUME OVERLOAD
DEPENDING ON WHETHER ENTERITITIS OR RENAL INSUFFICIENCY FROM HUS PREDOMINATE.
• PATIENT WITH PNEUMOCOCAL ASSOCIATED ARE QUITE ILL WITH PNEUMONIA EMPYEMA
AND BACTEREMIA
• PALLOR,LASSITUDE,DROWSINESS,OLIGURIA,HYPERTENSION.
• UNCOMMON FEATURE GROSS HAEMATURIA,PETECHIAE,PURPURA,JAUNDICE,WITH SEVERE
RENAL INVOLVEMENT
• THOSE WHO PRESENT LATE MAY HAVE NEUROLOGICAL INVOLVEMENT WITH CONVULSION
• D- HUS MOSTLY PRESENT IN OLDER CHILDREN AND HAVE NEPHROTIC RANGE PROTEINURIA
AND HEMATURIA AND HYPERTENSION.THIS TYPE OF PATIENT HAVE HIGHER CHANCE OF
DEVELOPMENT OF CHRONIC RENAL FAILURE

16. • THE COMBINATION OF RAPIDLY DEVELOPING RENAL FAILURE AND
SEVERE HEMOLYSIS CAN RESULT IN LIFE THREATENING
HYPERKALEMIA.
• SOME TIME PATIENT HAVE HYPOKALEMIA IN INITIAL PHASE DUE TO
LOOSE MOTION
• VOLUME OVERLOAD HYPERTENSION AND SEVERE ANEMIA
DEVELOP SOON AFTER ONSET OF HUS AND CAN PRECIPITATE
HEART FAILURE.
• PERICARDITIS,MAYOCARDIAL DYSFUNCTION OR ARRHYTHMIA CAN
DEVELOP WITHOUT PREDISPOSING FEATURE OF HYPERTENSION
VOLUME OVERLOAD OR ELECTROLYTE ABNORMALITY.
• MAJORITY OF PATIENT HAVE MILD MANIFESTATION OF CENTRAL
NERVOUS SYSTEM AND <20% PATIENT DEVELOP SEIZURE AND
SEVERE CNS MANIFESTATION DUE TO MICRO VASCULAR THROMBI
IN CNS AND SOME TIME PRESS DUE TO HYPERTENSION

17. PATHOLOGICAL FINDING
• RENAL BIOPSY FINDING IN HUS REPRESENT SEVERE END OF SPECTRUM
,SINCE THE USUAL COURSE OF HUS IN CHILDREN IS MILDAND ONLY THOSE
PATIENT WITH SEVERE ORPERSISTENT CLINICAL FEATURE UNDERGO
BIOPSY.
• MOST PATIENT WITHCLASSICAL D+ HUS DOES NOT REQUIRE A BIOPSY
AND MAY RECOVER WITH NO OR MINOR CLINICAL RESIDUE
• MICROSCOPIC FINDING OF RENAL BIOPSY DEPEND UPON AT WHICH
COURSE OF DISEASE BIOPSY IS TAKEN.
• EARLY STAGE-ACUTE LESION IS DEFINED AS THE PRESENCE OF AT
LEAST 1 FIBRIN MICROTHROMBI,EITHER IN GLOMERULI OR IN SMALL
ARTERIOLE AND/OR IN ARTERIES
• ISCHEMIC CHANGES IN GLOMERULI WITH ENDOTHELIAL SWELLING AND
CAPILLARY LUMINAL NARROWING
• FIBRINOID NECROSIS OF LARGE VESSELS,THROMBOSIS AND ENDOTHELIAL
CELL PROLIFERATION IN SMALL ARTERIESAND ARTERIOLES

18. • LATER STAGE-
• INTESNSE BASOPHILIC THICKENING IN SMALL ARTERIES AND ARTERIOLES
WHICH RESTRICTS LUMEN (ONION SKIN LESION),ANEURYSMAL
DILATATION AND PROLIFERATION OF ARTERILOES AT HILUS OF
GLOMERULUS
• MAY HAVE DOUBLE COUNTER OF GLOMERULA MEMBRANE

19. INVESTIGATION
COMPLETE BLOOD COUNTS,PERIPHERAL SMEAR FOR
SCHISTOCYTE,RETICULOCYTE COUNTS
LACTATE DEHYDROGENASE,HEPTOGLOBIN
DIRECT COOMB TEST
BLOOD:CREATININE,ELECTROLYTES,TRANSAMINASES,BILIRUBIN,
COMPLEMENT C3
URINANALYSIS
RAPID TEST FOR MALARIA DENGUE LEPTOSPIRA
COAGULATION PROFILE
ULTRASOUND ABDOMEN
IF CLINICAL FEATURE
PRESENT:ECHOCARDIOGRAM,NEUROIMAGING,AMYLASE,
TROPONIN T

20. • ESSENTIAL
• ANTI FACTOR H ANTIBODY,ANTINUCLEAR ANTIBODY
• CD 46 EXPRESSION ON NEUTROPHIL
• TOTAL HOMOCYSTINE
• STORE BLOOD FOR ADAMTS 13 ACTIVITY
• SELECTED PATIENT
• SUSPECTED SHIGA TOXIN ASSOCIATED HUS-STOOL SAMPLE FOR
CULTURE (SORBITOL,MACKONKY AGAR,SELECTIVE MEDIA)PCR FOR
STX1 STX2 AND ENTEROHEMOLYSIN GENE,ELISA FOR SHIGA
TOXIN,IGM ANTIBODY TO SPECIFIC LIPOPOLYSACCHARIDE
• SUSPECTED PNEUMOCOCCAL HUS-CULTURE,PCR OR ELISA,PEANUT
LECTIN AGGLUTINATION TEST
• SEQUENCING GENE-CFH,CFI,CFB,C3,CD46,DGKE,THBD,MMACHC

21. • INDICATION FOR RENAL BIOPSY
• UNCLEAR DIAGNOSIS OF HUS
• UNSATISFACTORY CLINICAL RESPONSE,TO
DETERMINE EXTENT OF RENAL DAMAGE AND
HELP IN PROGNOSIS
• DISTINGUES BETWEEN CAUSE OF ALLOGRAFT
DYSFUNCTION,INCLUDING RECURRENT HUS

22. • HAEMOLYTIC ANAEMIA-THE PERIPHERAL SMEAR SHAWS DEFORMED AND BROKEN RBC.THE CELLS
ARE FRAGMENTED AS THEY TRAVERSE THE MESHWORK OF FIBRIN STRAND IN THE
MICROVASCULATURE.INCREASED OXIDANT DAMAGE TO RBC MEMBRANE MAY ALSO PLAY A
ROLE.BACTERIAL NEURAMINIDASE AND PHOSPHOLIPASE C CAN INJURE ENDOTHELIAL CELL,RBC
AND PLATELET
• THROMBOCYTOPENIA-PLATELET COUNTS ARE INVARIABLY DECREASED AND RETURN TO NORMAL
IN 2 TO 3 WEEKS.THERE IS ENHANCED PLATELET CONSUMPTION, DUE TO CONTACT WITH
DAMAGED VASCULAR ENDTHELIU .THE PRODUCT OF PLATELET INJURY CAUSE NEUTROPHIL
CHEMOTAXIS.SERUM LEVEL OF SERATONIN AND PLATELET LEVEL 4 INCREASED.
• LEUKOCYTOSIS-ANEUTROPHILIC LEUKOCYTOSIS IS COMMON IN HUS,ESPECIALLY IN THE POST
DYSENTERIC FORM.ACTIVATED NEUTROPHILIC RELEASE LYSOSOMAL ENZYME AND REACTIVE
OXYGEN RADICALS THAT CAN CAUISE OR AGGRAVATE ENDOTHELIAL CELL DAMAGE
• COAGULATION-NORMAL LEVEL OF FIBRINOGEN AND NORMAL FIBRINOGEN TURN OVER SUGGEST
ABSCENCE OF DIC.RAISED LEVEL OF FDP INDICATE ACTIVATION OF THE FIBRINOLYTIC
SYSTEM.ENDOTHELIAL INJURY LEADS TO RELEASE OF LARGE VON WILLEBRAND FACTOR POLYMER
THAT CAUSE PLATELET AGGREGATION AND INCREASE FORMATION OF PLATELET THROMBI.
• BIOCHEMISTRY-BIOCHEMICAL CHANGES INDICATIVE OF RENAL DYSFUNCTION ARE
PRESENT.SERUM CONCENTRATION OF POTASSIUM IS LOW INITIALLY PERHAPS DUE TO LOSSES
DURING THE DIARRHOEAL PRODROME.URINE ANALYSIS SHAW RED CELL AND OCCASIONAL CASTE
CELL.

23. INVOLVEMENT OF OTHER ORGAN IN
HUS
• INVOLEVEMENT OF OTHER ORGAN ESPECIALLY
BRAIN AND PANCREAS SEEN.
• RARELY INVOLVEMNT OF HEART LIVER EXOCRINE
AND ENDOCRINE PANCREAS AND MUSCLE SEEN
• PERMANANT OR TRANSIENT INSULIN
DEPENDENT DIABETES MELLITUS OCCUR IN
SMALL PROPRTION
• MOST PATIENT WHO RECOVER DOES NOT SHAW
RESIDUAL ORGAN DEFECT EXCEPT KIDNEY

24. APPROACH TO HUS
SUSPECTED HEMOLYTIC UREMIC SYNDROME
RULE OUT SEPSIS,DIC,MALARIA,DENGUE,LEPTOSPIRA
CONSIDER PROBABALE OR CONFIRMED TTP
SHIGA TOXIN ASSOCIATED HUS
PROBABLE-BLOODY DYSENTERY OR OUTBREAK
PNEUMOCOCCAL HUS
HB <10,SCHISTOCYTES >2%,LDH
>450IU/L,HAPTOGLOBIN<30
MG/DL,PLATELET
<1,50,000,ACUTE KIDNEY INJURY
SUSPECTED-MILD AKI WITH
PERSISTENT
THROMBOCYTOPENIA
<30,000
CONFIRMED-ADAMTS 13
LEVEL <10% OR ANTIBODY TO
ADAMTS 13 PRESENT
CONFIRMED-DIRECT SCREENING
OF FECAL EXTRACT OR CULTURE
FOR SHIGA PCR OR ELISA FOR
TOXIN OR IGM ANTIBODY TO
SPECIFIC LIPOPOLYSACCHARIDE
PROBABABLE-<2YEAR WITH
SEPSIS,PNEUMONIA,MENINGITIS AND
POSITIVE DCT
CONFIRM-POSITIVE BLOOD CULTURE OR PCR
OR ELISA IN BODY FLUIDS

25. HUS WITH OTHER INFECTION
COBALAMINE C DEFICIENCY HUS
SECONDARY HUS
EVALUATION FOR ATYPICAL HUS
ELEVATED
HOMOCYSTEINE
LEVEL AND MMACHC
GENE MUTATION
SLE,APLA,DRUG
INDUCED,MALIGNANCY,MALIGN
ANT HYPERTENSION,ORGAN
TRANSPLANT
C3,GENETIC
SCREENING,CD 46
CYTOMETRY,ANTI FACTOR
H ANTIBODY

26. TTP OR HUS OR SOMETHING ELSE !

27. • TTP-PENTAD
• FEVER
• NEUROLOGICAL MANIFESTATION
• MICROANGIOPATHY
• THROMBOCYTOPENIA HUS TRIAD
• RENAL INVOLVEMENT
• 60% PATIENT OF TTP LACKS ONE OR MORE OF PENTAD
• 30%HUS PATIENT HAVE FEVER AND NEUROLOGICAL
SYMPTOMS
• IF PLATELETS >30000 AND CREATININ >2 ITS LESS LIKELY TO
BE TTP
• ADAMTS >10% RULE OUT TTP

30. • EVAN YNDROME-
• AIHA+ITP
• AIHA CAN BE WARM IgG OR COLD IgM
• IF THE SMEAR DOES NOT SHAW SCHICTOCYTE BUT INSTEAD SHAW
SPHEROCYTOSIS OR RED CELL AGGLUTINATION
• LDH HIGH AND HAPTO LOW
• DCT POSITIVE
• HEMOGLOBINURIA ONLY IN COLD AIHA
• CONGENITAL TTP-UPSHAW SCHULLMAN SYNDROME
• MAHA AND JAUNDICEIN IN NEONATE
• IN CHILDREN UNEXPLAINED THROMBOCYTOPENIA
• ADAMTS 13 LEVEL <5%
• ABSCENCE OF ANTIBODY TO ADAMTS 13

31. • COULD THIS BE A DIC-LESS LIKELY GIVEN THE
DISCONNECT BETWEEN THE SEVERITY OF
THROMBOCYTOPENIA AND THE PATIENT
CLINICAL PRESENTATION.WOULD NEED
PT,PTT,FIBRINOGEN
• COULD THIS BE ITP-NORMAL LDH AND
HAPTOGLOBIN
• COULD THIS BE A LEUKEMIA-PERIPHERAL
SMEAR WOULD GIVE ANSWER

32. • FACTS ABOUT ADAMTS 13
• <10% IS SPECIFIC FOR PATUIENT WITH IMMUNE
MEDIATED OR CONGENITAL TTP
• ADAMTS CAN BE MILDLY OR MODERATELY
DECREASE WITH INFLAMMATION,HEPATIC
DYSFUNCTION AND PREGNANCY
• IF ADAMTS ACTIVITY IS <30% THE INHIBITOR
ASSAY IS PERFORMED
• SAMPLE SHOULD BE DRAWN BEFORE
CRYOPRECIPITATE OR PLASMA INFUSION

33. TREATMENT
THE PRIMARY APPROACH THAT HAS SUBSTANTIALLY IMPROVED AN ACUTE OUTCOME IN HUS IS
EARLY RECOGNITION OF THE DISEASE,MONITORING FOR POTENTIAL COMPLICATION AND
METICULOUS SUPPORTIVE CARE.
SUPPORTIVE CARE INCLUDE CAREFUL MANAGEMENT OF FLUID AND ELECTROLYTE INCLUDING
PROMPT CORRECTION OF VOLUME DEFICIT,CONTROL OF HYPERTENSION AND EARLY
INSTITUTE OF DIALYSIS IF PATIENT BECOME SIGNIFICANTLY OLIGURIC OR
ANURIC,PARTICULARLY WITH HYPERKALEMIA.
EARLY INTRAVENOUS VOLUME EXPANSION BEFORE THE ONSET OF OLIGURIA OR ANURIA MAY BE
NEPHROPROTECTIVE IN DIARRHOEA ASSOCIATED HUS.
RED CELL TRANSFUSION IF HB <6 GM% REQUIRED BECAUSE HEMOLYSIS IS BRISK AND
RECURRENT UNTIL ACTIVE PHASE SUBSIDE.
FOLATE SUPPLEMENT SHOULD BE STARTED
PLATELET SHOULD BE NOT TRANSFUSED REGARDLESS OF PLATELET COUNTS.BECAUSE RAPIDLY
CONSUMED BY ACTIVE COAGULATION AND WORSEN THE CLINICAL COURSE.
ANTIBIOTIC WHICH IS CONTROVERSIAL
PLASMAPHARESIS IN SEVER MANIFESTATION
ANTICOAGULANT ANTIPLATELET AND ANTIFIBRINOLYTIC DOES NOT HAVE ANY ROLE AND MAY
CAUSEHAEMORRHAGE
CARE OF NUTRITION AND OTHER MANIFESTED SYMPTOMS SHOULD BE TAKEN

34. • THERAPY FOR PNEUMOCOCCAL ASSOCIATED HUS
• PLASMA PHARESIS CONTRAINDICATED BECAUSE IT COULD EXACERBATE
DISEASE DUE TO ENDOGENEOUS IGM IN PLASMA
• RED CELL TRANSFUSION IS CRITICAL HERE BECUSE IT SHOULD BE
WASHED TO REMOVE PLASMA
• ANTIBIOTIC IS RECOMMENDED
• THERAPY FOR ST-HUS
• RED CELL TRANSFUSION RECOMMENDED
• PLASMA PHARESIS WHO HAVE NEUROLOGICAL OR CARDIOLOGICAL
MANIFESTATION
• ANTIBIOTIC IS CONTROVERSIAL AS O104:H4 OUTBREAK IN EUROPE
AZITHROMYCIN DEMONSTRATED MORE RAPID ELIMINATION OF
ORGANISM EVEN MEROPENEM RIFAXIMIN AND AZITHROMYCIN
DOWNREGULATE THE RELEASE OF SHIGA TOXIN.
• BUT NELSON DOES NOT RECOMMEND ANTIBIOTIC IN STEC-HUS

35. • THERAPY FOR ATYPICAL HUS WITHOUT ANTI FH
ANTIBODY
• PROMPT PLASMA EXCHANGE WITHIN DIAGNOSIS OF
24 HOUR
• DAILY PLASMA EXCHANGE UNTIL HAEMATOLOGICAL
REMISSION THAN TAPER OVER 4-6 WEEK
• CONSIDER ECULIZUMAB IF REFRACTORY TO 7-10
PLASMA EXCHANGE OR LIFE THREATENING
MANIFESTATION LIKE SEIZURE CARDIAC
DYSFUNCTION,COMPLICATION OF PLASMA EXCHANGE
OR INHERITED DEFECT IN COMPLEMENT REGULATION

36. MANAGING
ANTI FH ANTIBODY
ASSOCIATED AHUS

37. PROTOCOL FOR PLASMA EXCHANGE
OR INFUSION
• METHOD-MEMBRANE FILTRATION OR CENTRIFUGATION
• REPLACEMENT FLUID-FRESH FROZEN PLASMA
• ANTICOAGULANT-HEPARIN OR CITRATE
• INTRAVENOUS PREMEDICATION-PHENIRAMINE AND HYDROCORTISONE
• MAINTAIN IONISED CALCIUM >1 AND POTASSIUM 3.5 TO 5.5
• SCHEDULE- DAILY WITH 1.5 TIME PLASMA VOLUME PER SESSION FOR 5 DAYS OR
TILL REMISSION WHICHEVER IS LONGER
• THAN ALTERNATE DAY 40 ML/KG FOR 2 WEEK
• THAN TWICE A WEEK FOR 2 WEEK
• ANTI FH NEGATIVE HUS-PENDING GENETIC STUDY-CONTINUE PLASMA INFUSION
AFTER 6-8 WEEK OF EXCHANGE 10-20 ML/KG ONCE EVERY 7-10 DAYS
• ANTI FH POSITIVE HUS-STOP PLASMA EXCHANGE AFTER 6 WEEK
• CD46 OR DGKE VARIANT STOP EXCHANGE TRANSFUSIOM
• CFH,CFI,CFB,C3,THBD VARIANT LONG TERM PLASMA INFUSION WITH
ECULIZUMAB

38. ECULIZUMAB
• COST 2.5 LAKH PER VIAL OF 300MG
• C5 INHIBITOR
• CONTRAINDICATED IN CNS INFECTION
• GIVE MENINGOCOCCAL VACCINE 2 WEEK PRIOR

39. • DEFINATION OF RESPONSE
• HEMATOLOGICAL REMISSION-PLATELET >1LAKH
SCHISTOCYTES <@%,LDH LESS THAN UPPER LIMIT
OF NORMAL ON 2 CONSECUTIVE DAYS
• RELAPSE:RECURRENCE OF ANEMIA WITH
SCHISTOCYTES >2% ELEVATED LDH AND OR
THROMBOCYTOPENIA WITH OR WITHOUT AKI
FOLLOWING REMISSION FOR >2 WEEK
• REFRACTORY ILLNESS-PLATELET <1LAKH OR
PERSISTENT HEMOLYSIS DESPITE 7-10 DAYS DAILY
ADEQUATE PLASMA EXCHANGE

41. RENAL TRANSPLANT IN HUS
• PATIENT WITH A-HUS SHAW VARIABLE RISK OF
RECURRENCE IN THE ALLOGRAFT TRANSPLANT
• RECEPIENT SHOULD BE SCREEN FOR ANTI FH ANTIBODY
• BETTER RESULT IN ST-HUS AND CD46 AND DGKE HUS
• RECURRENCE RISK IS HIGH IN DYSREGULATION IN
ALTERNATE PATHWAY
• LIVE RELATED DONOR SHOULD BE AVOIDED IN PATIENT
WITH HIGH RISK OF DISEASE RECURRENCE.SUCH PATIENT
REQUIRE EITHER COMBINED LIVER KIDNEY
TRANSPLANTATION OR THERAPY WITH ECULIZUMAB PERI
AND POST TRANSPLANT AT AN APPROPRIATE CENTRE

42. PROGNOSIS
• MORTALITY RATE FOR DIARRHOEA ASSOCIATED HUS IS
<5%.IN MOST CENTRE UP TO HALF PATIENT REQUIRE
DIALYSIS DURING ACUTE PHASE
• PNEUMOCOCCI ASSOCIATED HUS REQUIRE DIALYSIS >80%
AND MORTALITY RATE IS >20%
• GENETIC OR FAMILIAL FORM OF HUS HAVE INSIDIOUSLY
PROGRESSIVE AND RELAPSING COURSE AND POOR
PROGNOSIS
• DURING RECOVERY PHASE 1ST THING TO RECOVER IS
PLATELET FOLLOWED BY RENAL RECOVERY AFTER 5 DAY
AND RESOLUTION OF ANAEMIA
• OVER ALL 5% REMAIL ON DIALYSIS AND 30% SOME
CHRONIC RENAL INSUFFICIENCY

43. FOLLOW UP
ALL PATIENT REQUIRE FOLLOW UP FOR 5 YEAR
FOR HYPERTENSION PROTEINURIA AND
ESTIMATED GFR.
PATIENT AND FAMILY SHOULD BE COUNSEL
ABOUT RISK OF RELAPSE.
INITIALLY CLOSE FOLLOW UP FOR MONTHLY
AND THAN IF 1 YEAR PERIOD OF REMISSION
PASS THAN YEARLY FOLLOW UP

44. THANK YOU