Dr. E.SUDHA (Fellow in Pediatric Nephrology) DEPT OF PEDIATRIC NEPHROLOGY & DIALYSIS Dr.MEHTA CHILDRENS HOSPITAL
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1 Dr. E.SUDHA (Fellow in Pediatric Nephrology) DEPT OF PEDIATRIC NEPHROLOGY & DIALYSIS Dr.MEHTA CHILDRENS HOSPITAL
2 CASE HISTORY 4 yrs old previously well boy Born to 2 nd degree consanguinity Fever x 5 days Edema, pallor, UOP x 3 days PRBC transfused outside 4gm% Diagnosed as renal failure Referred
3 ON EXAMINATION Anasarca + BP - 140/100 mm Hg CVS - Short systolic murmur RS - Air entry on right side Abd - Ascites+, no organomegaly CNS - Essentially normal
4 INVESTIGATIONS TC : 14,700 cells/mm 3 DC : P80L18E2 Hb : 7.7 g% PLATELET COUNT : 1.0 lakhs/mm 3 Peripheral Smear: features suggestive of hemolytic anemia (schistocytes, burr cells, helmet cells)
5 INVESTIGATIONS S.Cr: 5.8 mg/dl S.Na: 125 meq/dl S.K: 4.8 meq/dl S.HCO3: 18 meq/dl S.Ca: 8.4 mg/dl S.Alb: 2.6 mg/dl S.chol: 155 mg/dl LDH: 8050 U/L
6 INVESTIGATIONS (cont ) Bld & urine C/S NG PT & PTT Normal C3 1.5 g/l ( ) CXR Pleural fluid right USG abd B/L renomegaly with increased cortical echogenecity ECHO Normal
7 PROVISIONAL DIAGNOSIS Hemolytic Anemia Thrombocytopenia Renal failure ATYPICAL HEMOLYTIC UREMIC SYNDROME
8 TREATMENT Fluid modulation Salt restriction Anti hypertensives (nifedepine,atenolol,hydralazine) IV antibiotics
9 TREATMENT Internal Jugular access obtained 8Fr size Hemodialysis 4 sessions Plasmapheresis 6 sessions 30ml/Kg plasma removed & replaced with FFP at each session
10
11 COURSE IN THE HOSPITAL Date S.Cr Hb Plt LDH BP UOP (1HD) (3HD,3PE) /100 10ml /100 55ml / ml (4HD,5PE) /70 510ml (4HD,6PE) /70 875ml
12 OUTCOME Improved & discharged after 15d On follow up - normal
13
14 DEFINITION Hemolytic uremic syndrome is the triad of Microangiopathic hemolytic anemia, Thrombocytopenia, Acute renal injury
15 CLASSIFICATION D + HUS (Typical) D - HUS (Atypical) 1) Infection Strep Pneumoniae 2) Disorder of complement regulation (CFH,CFI,CFB.MCP) 3) vwb proteinase def (ADAMTS13) 4) SLE 5) Drug induced (Quinine, Calcineurin inhibitor) 6) Others Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol, 2008 : 23;
16 D + HUS Post diarrhoeal HUS - 90% STEC 6 months to 3 years of age Favourable outcome 75% patients - long term full recovery Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol, 2008 : 23 ;
17 D - HUS Seen in 10% of children Occurs any age Sporadic or familial Poor prognosis - 50% progress to ESRD Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol, 2008 : 23 ;
18 COMPLEMENT MUTATION Due to absence of CFH & its cofactors Uncontrolled activation of alternative complement pathway Excess C3 convertase formed Formation of inflammatory mediators Endothelial damage & microangiopathic lesion Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol, 2008 : 23 ;
19 PATHOPHYSIOLOGY Pediatr Nephrol, 2008 : 23 ;
20 ADAMTS 13 DEFICIENCY ADAMTS 13 cleaves Vwf Absence leads to large multimeric form of vwf Continuous platelet aggregation TMA HUS.Indian Pediatr 2009;46:
21 PATHOGENESIS
22 Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol, 2008 : 23 ; TREATMENT Plasmatherapy plasma exchange/plasma infusion Dialysis Antihypertensives
23 PLASMAPHERESIS Large quantities of plasma are removed Replaced with fresh frozen plasma (FFP) or albumin.
24 PLASMAPHERESIS blood circuit Apheresis Filter or centrifuge Replace ment Fluid access Patient Plasma Cell Concentrate Reconstituted Blood
25 INDICATIONS Hemolytic Uremic Syndrome Gullian-Barre Syndrome Practical considerations for planning therapeutic Apheresis procedure. The American Journal of Medicine, 2010 : 123 ;
26 REPLACEMENT FLUIDS Advantages Albumin FFP No risk of hepatitis. Allergic reactions are rare. No concern about blood group. Depletes inflammatory mediators Adds coagulation factors, immunoglobulins, complements.
27 REPLACEMENT FLUIDS Dis-advantages Albumin FFP Expensive No coagulation factors No IG Risk of hepatitis, HIV Allergic reactions, hemolytic reactions Must be thawed Citrate load Must be blood group compatible
28 COMPLICATIONS Related to vascular access. Hematoma, Pneumothorax Related to procedure. Hypotension, Hypersensitivity reactions Related to anti-coagulation. Hypocalcemia
29 TAKE HOME MESSAGE Extracorporeal blood purification therapy Can be easily performed with dialysis machines Though HUS is an aggressive disease, this therapy is a good modality & leads to less morbidity and mortality.
30 LITERATURE REVIEW Practical considerations for planning therapeutic Apheresis procedure. The American Journal of Medicine, 2010 : 123 ; Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol, 2008 : 23 ; The thrombotic microangiopathies. Pediatr Nephrol, 2008 : 23; Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol, 2008 : 23;
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