Microangiopathic haemolytic anaemia with a normal coagulation screen
A 34-year-old woman presents with three days of fever, confusion and bruising. She takes no regular medication and has no recent travel. Temperature 38.4 °C, blood pressure 128/76 mmHg, pulse 96, petechiae over both shins and oozing from venepuncture sites. Bloods: haemoglobin 7.8 g/dL, MCV 92 fL, white cells 11.2 × 10^9/L, platelets 9 × 10^9/L, reticulocytes 6%, LDH 1450 U/L, haptoglobin low, bilirubin 42 micromol/L, creatinine 180 micromol/L, INR 1.05, APTT 28 s, fibrinogen 3.2 g/L. Blood film shows schistocytes. ADAMTS13 has been sent and is pending.
1. How do the coagulation results help you distinguish thrombotic thrombocytopenic purpura from disseminated intravascular coagulation, and what would you do while the ADAMTS13 result is pending?
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The coagulation screen is the key discriminator. In DIC, factors are consumed: INR and APTT prolong, fibrinogen falls, D-dimer rises, and the film may show schistocytes. Here INR 1.05, APTT 28 s and fibrinogen 3.2 g/L are essentially normal, which argues strongly against DIC and points to a primary microangiopathy - TTP or complement-mediated HUS. Severe ADAMTS13 deficiency (below 10%) defines TTP.
Normal coagulation does not exclude sepsis or malignancy, but the combination of microangiopathic haemolytic anaemia, platelets 9 ×10^9/L, neurological symptoms, fever and renal impairment is the classic pentad; in practice, do not wait for all five.
While ADAMTS13 is pending:
- Start urgent plasma exchange (1–1.5 plasma volumes daily) with fresh frozen plasma replacement plus high-dose corticosteroids (methylprednisolone 1 g daily for three days or prednisolone 1 mg/kg). Do not wait for the result if the clinical picture fits.
- Avoid platelet transfusion unless there is life-threatening bleeding; transfused platelets can worsen microvascular thrombosis.
- Send blood cultures, HIV and hepatitis serology, a pregnancy test, and ask a haematologist to review the film. Take a drug history (ticlopidine, quinine, calcineurin inhibitors).
- Correct anaemia with packed cells if symptomatic; use leucodepleted products.
- Involve haematology and apheresis immediately; if plasma exchange is unavailable, give fresh frozen plasma while arranging transfer.
The reasoning: the risk of delaying plasma exchange in TTP (mortality above 90% untreated) far outweighs the risk of treating a mimic.
2. She needs a central venous catheter for plasma exchange. Discuss your transfusion and procedural decisions, with the reasoning behind them.
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This is a procedural risk decision, and the default is to avoid platelet transfusion.
- Platelets: In TTP, platelets are consumed in microthrombi. Transfusion may increase thrombotic events and is reserved for life-threatening haemorrhage or, in some centres, for an urgent invasive procedure with a very low count. For central line insertion, use ultrasound guidance, a single experienced operator and prolonged compression after. Many centres would insert with a platelet count around 10–20 ×10^9/L without prophylactic transfusion because the bleeding risk is small compared with the thrombotic risk; some would give one pool immediately before the procedure if the count is below 20 ×10^9/L and the operator judges bleeding risk high. This should be a senior decision, documented.
- Red cells: Transfuse to a target haemoglobin of 70–80 g/L, or higher if she is symptomatic or has cardiac disease; use leucodepleted products. Avoid over-transfusion, which raises viscosity.
- Plasma: Plasma exchange is the treatment; do not give fresh frozen plasma as a volume expander outside exchange unless exchange is delayed.
- Other: Avoid intramuscular injections, aspirin and NSAIDs; hold antiplatelet agents. Coordinate the timing of line insertion and first exchange with the apheresis team.
- If she bleeds massively, transfuse platelets and red cells together and treat as an emergency.
The judgement is to weigh a small procedural bleeding risk against a real thrombotic risk, and to escalate the decision rather than defaulting to a platelet pool.