Haemolytic uremic syndrome

hus, pediatric diarrhoea with thrombocytopenia

1. Haemolytic U remic Syndrome (HUS) Dr. Virendra Kumar Gupta Assistant Professor Department Of Pediatric Gastroentero-hepatology & Liver Transplantation NIMS Medical College & Hospital , Jaipur

2. DEFINITION HUS is a clinical syndrome that destroys red blood cells, is the most common cause of sudden, short-term acute kidney failure in children. It is a triad of: Micro- angiopathic hemolytic anemia (MAHA) Thrombocytopenia. Acute kidney injury (acute renal failure) A clinical syndrome

3. Most common cause of acute renal failure in children and is increasingly recognized in adults. First described by Gasser et al in 1955.

4. CLASSIFICATION OF HUS / TTP ACCORDING TO ETIOPATHOGENESIS Type of HUS / TTP Specific Cause Infection related Shiga toxin producing E.coli / Shigella Pneumococcal infection HIV Typical Other viral or bacterial infections Complement factor abnormality Factor H deficiency CTD Factor I deficiency Miscellaneous Drugs Atypical Malignancy

5. Two main categories of HUS Shiga-like toxin associated HUS (Stx-HUS) Non-shiga-like toxin associated HUS (non-Stx-HUS)

6. Stx-HUS: (tHUS) D+ HUS D- HUS Non-StxHUS: (aHUS) Sporadic Familial

7. Stx-associated HUS In developed countries: Escherichia coli serotype O157:H7 (EHEC) most common. In developing countries: Shigella dysenteriae serotype 1.

8. Source of infection Human feco-oral transmission. Milk and animal products (incompletely cooked) Veges, salads,drinking water contaminated by bacteria shed in animal wastes.

9. Pathogenesis Shiga-like toxin affects endothelial cells and initiates intravascular thrombo -genesis . After entering the circulation via the gastrointestinal mucosa, the toxin preferentially localizes to the kidneys, inhibiting protein synthesis and eventually leading to cell necrosis or apoptosis. Endothelial cell damage subsequently potentiates renal microvascular thrombosis by promoting activation of the blood coagulation cascade . Platelet aggregation results in a consumptive thrombocytopenia . Microangiopathic hemolytic anemia results from mechanical damage to red blood cells circulating through partially occluded microcirculation.

10. Histopathological hallmark of HUS Thrombotic microangiopathy (TMA) Characterized by: Capillary endothelial damage. Microvascular formation of platelet/fibrin plugs. This induces tissue ischemia Damage to erythrocytes Consumptive thrombocytopenia.

11. ADAMTS-13 deficiency Familial: usually in children. rare. Acquired: more common in adults and older children. Associated with presence of anti-ADAMTS13 antibodies. Manifestation classically of frank TTP.

12. CLINICAL FEATURES The commonest clinical presentation of HUS is : Acute pallor Oliguria Diarrhea or dysentery It occurs commonly in children between 1-5 years of age HUS develops about 5-10 days after onset of diarrhea

13. CONTI.. Hematuria and hypertension are common. Complications of fluid overload may present with: Pulmonary edema Hypertensive encephalopathy Despite thrombocytopenia, bleeding manifestations are rare Neurological symptoms like: Irritability Encephalopathy Seizures

14. INVESTIGATIONS CBC Peripheral blood smears Reticulocyte count LDH Bili unconjigated Cr & BUN Urine analysis Hemoglobinuria Hematuria Proteinuria

15. Schistocytes

16. Investigations to Identify Cause In patients with dirrhea , the identification of pathogenic EHEC or Shigella is performed by: Stool culture Further serotyping by agglutination or enzyme immunoassay Rarely HUS can occur with E. coli UTI: Urine cultures are indicated in non-diarrheal patients

17. Conti.. Bacteriological cultures of body fluids are indicated in suspected pneumococcal disease. Sputum CSF Blood Pus

18. Diagnosis Clinically, HUS can be very hard to distinguish from TTP The laboratory features are almost identical , and not every case of HUS is preceded by diarrhea HUS is characterized by the triad of: Hemolytic anemia Thrombocytopenia Acute renal failure

19. Cont… The only distinguishing feature is that in TTP fever and neurological symptoms are often present, but this is not always the case A pericardial friction rub can also sometimes be heard on auscultation The two conditions are sometimes treated as a single entity called TTP/HUS.

20. MANAGEMENT Supportive Therapy Antibiotics Plasma Therapy Miscellaneous

21. Supportive Therapy In all patients, supportive treatment is primary. Close clinical monitoring of : Fluid status Blood pressure Neurological Ventilatory parameters Blood levels of glucose , electrolytes , creatinine and hemogram need frequent monitoring

22. CONTI.. The use of antimotility therapy for diarrhea has been associated with a higher risk of developing HUS With the onset of acute renal failure : Fluid restriction Diuretics

23. Antibiotics E. coli Shigellosis pneumococcal HUS

24. Plasma Therapy In aHUS due to : complement factor abnormality ADAMTS13 deficiency The replacement of the deficient factor with FFP Daily plasma infusions ( 10 to 20 mL /kg/day) Exchange of 1.5 times plasma volume ( 60 to 75 mL /kg/day) using FFP

25. Miscellaneous In infants with HUS associated with cobalamin abnormalities: Treatment with hydroxycobalamin Oral betaine Folic acid Normalizes the metabolic abnormalities can help to prevent further episodes.

26. CONTI.. In patients with persistent ADAMTS13 antibodies and poor response to plasma exchange: Immunosuppressive therapy with high dose steroids/ cyclophosphamide / cyclosporin / rituximab Splenectomy

27. Prevention Once patient infected with EHEC, attempts to prevent progression from bloody diarrheal phase to postdiarrheal phase of HUS have been unsuccessful. Antibiotics and anti-motility drugs not recommended. Vigorous fluid repletion during diarrheal phase of illness is associated with less severe renal involvement.

28. Prognosis Hematologic manifestation resolve usually within one to two weeks. Mortality rate <5%. Causes of death include hyperkalemia, CHF, pulmonary hemorrhage.

29. Markers of poor prognosis WCC>20 on presentation Persistent oliguria/anuria. Renal histology showing a glomerular microangiopathy affecting >50% of glomeruli, arterial microangiopathy +/- cortical necrosis.

30. Complications GASTROINTESTINAL NEUROLOGIC RENAL Intestinal strictures/perforations Intussusception Pancreatitis Severe colitis Altered mental status Focal neurologic signs Seizures Chronic renal failure Hematuria Hypertension Proteinuria

31. DIFFERNTIAL DIAGNOSIS Acute abdomen Acute gastroenteritis Appendicitis Colitis Disseminated intravascular coagulation Inflammatory bowel disease Lupus Thrombotic thrombocytopenia

32. summary HUS is a clinical syndrome characterized by MAHA, ARF and Thrombocytopenia. Thrombotic Microangiopathy (TMA) is the hallmark of disease pathogenesis. Stx or Non- Stx associated HUS. E.coli O157:H7 most common cause for Stx HUS. Strep pneumoniae for non- STx HUS. Familial form of HUS usually associated with complement dysregulation . Treatment of StxHUS mainly supportive with a good prognosis .

33. KEY MESSAGES Good sanitation and maintenance of food hygiene can prevent diarrhea associated HUS . Supportive care with early dialysis support remains the cornerstone of management. Non-infective atypical HUS should be treated rapidly with plasma therapy . Efforts should be made to make an etiological diagnosis in cases of atypical HUS as treatment and prognosis is affected.

34. THANKS