Haemolytic Uraemic Syndrome (H.U.S.)
Micro-angiopathic anaemia due to haemolytic uraemic syndrome. This is an uncommon presentation in clinical practice and if the blood film is not interpreted properly can easily be misdiagnosed as sepsis with multi-organ failure. Thrombotic thrombocytopenic purpura is an allied condition with similar pathological features. However, CNS manifestations predominate in this condition.
Discussion Haemolytic Uraemic Syndrome (H.U.S.)
Thrombotic microangiopathies are a rather uncommon presentation in clinical practice. Nevertheless, they do present in acute medical care and if the blood film is not interpreted properly, may be misdiagnosed as septicaemia with DIC, viral infection with multi-organ failure and malaria with multi-organ failure. The basic features are Fever, thrombocytopenia, progressive renal impairment, jaundice.
In thrombotic thrombocytopenic purpura, in addition, CNS manifestations predominate. Biochemical tests show high urea, creatinine, high bilirubin, high LDH (due to tissue necrosis rather than haemolysis). Blood film is very characteristic with a presence of fragmented and misshaped RBCs which is due to the passage of blood through the obstructed circulation (by platelet aggregates).
Haemolytic uraemic syndrome
- Predominant renal failure
- Often preceded by gastroenteritis caused by verocytotoxin producing E. coli 0157: H7 and exposure to shigella toxin
- Similar kind of feature may be found in patients receiving mitomycin, cyclosporin, tacrolimus, quinine, metronidazole post bowel surgery
Method Haemolytic uraemic syndrome
The bacterial toxins stimulate the endothelial cells to secrete unusually large multimers of Von Willebrand factor. This, in turn, leads to platelet aggregation in the peripheral circulation leading to microthrombi.
In familial haemolytic uraemic syndrome, there is also a deficiency of factor H, a plasma protein which prevents the normal host cells from the accidental damage of the endothelial cells by the activation of alternative complement pathway. In deficiency of factor H, there is activation of alternate complement pathway thereby leading to host cell damage; aggregation of platelets and formation of platelet microthrombi.
In haemolytic uraemic syndrome, plasma exchange or plasma infusion may be tried with equivocal results. Antimotility agents will increase production of bacterial toxins and should be avoided. Supportive therapy like renal replacement therapy should be instituted as per the requirement of the patient.
Thrombotic thrombocytopenic purpura
- Predominant CNS manifestation
- There may be familial, chronic relapsing variety
- Ticlopidine and clopidogrel can rarely cause TTP
Method Thrombotic thrombocytopenic purpura
Multimers of Von Willebrand factor are cleaved into monomeric subunits by an enzyme called ADMTS13. TTP may be acquired or hereditary (relapsing) also called Upshaw-Schulman syndrome is usually due to ADAMTS 13 mutation while acquired. TTP is due to autoantibody-mediated inhibition of ADMTS activity. In TTP, the enzyme ADMTS 13 is deficient. Infusion of fresh plasma may replace the deficient enzyme. There may be antibody formation against ADMTS13
In some cases, if the antibody titre is high immunosuppressive therapy with steroids and splenectomy may be needed. Platelet transfusion should be avoided. It will aggravate formation of platelet microthrombi. However, if there is obvious bleeding, it will be unavoidable. The role of aspirin in the face of bleeding is controversial. Other drugs used in refractory cases are vincristine, rituximab (experimental)
Any patient presenting with features of microangiopathic haemolytic anaemia features (either TTP or HUS) should be presumed to have TTP and treated with plasma exchange
The first patient described above had daily plasma infusions, needed regular blood and platelet transfusion, (she had gastrointestinal bleeding) and received peritoneal dialysis
After a long stay in the hospital, she was discharged home and 6 months at follow up her renal function had returned back to normal.
The second patient had a delayed presentation. Although she received plasma infusion, steroids, renal replacement therapy with haemodialysis, she progressively deteriorated and finally expired.