Thrombotic thrombocytopenic purpura

Definition

Fulminant disease of unknown aetiology characterised by increased platelet aggregation and occlusion of arterioles and capillaries of the microcirculation. Considerable overlap in pathophysiology and clinical features with HUS—fundamental abnormality may be identical.

Incidence:

Rare, ~1 in 500,000 per year. 3:9 = 2:1. HUS much commoner in children, TTP commoner in adults—peak age incidence is 40 years, and 90% of cases <60 years old. There is some case clustering.

Clinical features

• Classical description is of a pentad of features:

1. Microangiopathic haemolytic anaemia.

2. Severe thrombocytopenia.

3. Neurological involvement.

4. Renal impairment.

In practice, few patients have the full monty. 50-70% have renal abnormalities (cf nearly all with HUS) and they are less severe. Neurological involvement is more prevalent in TTP than HUS. 40% of TTP patients have fever.

• Haemolysis—severe and intravascular causing jaundice.

• Thrombocytopenia—severe, mucosal haemorrhage likely and intracranial haemorrhage may be fatal.

• Neurological—from mild depression and confusion—^visual defects, coma and status epilepticus.

530 • Renal—haematuria, proteinuria, oliguria and 4 urea and creatinine. HUS>TTP.

• Fever—very variable, weakness and nausea common.

• Other disease features: serious venous thromboses at unusual sites (e.g. sagittal sinus—microthrombi in the brain seen on MRI scan). Abdominal pain severe enough to mimic an acute abdomen is sometimes seen due to mesenteric ischaemia. Diarrhoea is common, particularly bloody in HUS.

Diagnosis and investigations

• Made on the clinical features above—exclude other diseases e.g. cerebral lupus, sepsis with DIC.

• FBC shows severe anaemia and thrombocytopenia.

• Blood film shows gross fragmentation of red cells, spherocytes and nucleated red cells with polychromasia.

• Clotting screen including fibrinogen and FDPs usually normal (cf. DIC).

• Serum haptoglobin low or absent.

• Urinary haemosiderin +ve.

• Unconjugated bilirubin 4.

• BM hypercellular.

• Proteinuria and haematuria.

• Renal biopsy shows microthrombi.

• Stool culture for E coli 0157 +ve in most cases of HUS in children, less often in adult TTP.

• MRI brain scan shows microthrombi and occasional intracranial haemorrhage.

• Lumbar puncture-do not proceed with LP unless scans clear and there is suspicion of infective meningitis.

• Look for evidence of viral infection. Association of syndrome with HIV, SLE, cyclosporin usage and the 3rd trimester of pregnancy.

Treatment is a haematological emergency—seek expert help immediately

1. Unless antecubital venous access is excellent, insert a large bore central apheresis catheter (may need blood product support).

2. May need ITU level of care and ventilation.

3. Initiate plasmapheresis as soon as possible.

Exchange 1-1.5 x plasma volume daily until clinical improvement. May need 3-4L exchanges. Replacement fluid should be solely FFP. In the event of delayed access to cell separator facilities, start IV infusions of FFP making intravascular space with diuretics if necessary. Once response achieved, 5 frequency of exchanges gradually. If no response obtained within one week, change FFP replacement to cryosupernatant (rationale: it lacks high molecular weight multimers of von Willebrand factor postulated in endothelial damage disease triggers). 531

4. Give RBC as necessary but reserve platelet transfusions for severe mucosal or intracranial bleeding as reports suggest they may worsen the disease.

5. Cover for infection with IV broad spectrum antibiotics including teicoplanin if necessary to preserve the apheresis catheter.

6. Start anticonvulsants if fitting.

7. Most would start high dose steroids (prednisolone 2mg/kg/d PO) with gastric protection although evidence is equivocal.

8. Aspirin/dipyridamole/heparin may be considered for non-responders.

9. Refractory patients (~10%) should be considered for IV vincristine.

10. Still refractory patients may achieve remission with splenectomy.

11. Response to treatment may be dramatic e.g. ventilated, comatose patient watching TV in the afternoon after plasma exchange in the morning!

Prognosis

• 90% respond to plasma exchange with FFP replacement.

• ~30% will relapse. Most respond again to further plasma exchange but leaves 15% who become chronic relapsers.

• Role of prophylaxis for chronic relapsers unclear. Intermittent FFP infusions or continuous low dose aspirin may help individual cases.

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