Thrombotic thrombocytopenic purpura (TTP)

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How the diagnosis is reached

Schistocytes with a high LDH, low haptoglobin and a negative Coombs test establish that red cells are being destroyed mechanically rather than by antibody: they are being physically sheared, not marked for removal. Pair that with severe thrombocytopenia and the differential is short, and the discriminators are all present here. Normal PT, aPTT and fibrinogen argue against disseminated intravascular coagulation, where the clotting cascade is consumed wholesale. Renal impairment that is only mild, with neurological signs that fluctuate, argues for thrombotic thrombocytopenic purpura over haemolytic uraemic syndrome, in which renal failure dominates and a diarrhoeal illness usually precedes it. The mechanism explains every finding at once. ADAMTS13 normally cleaves ultra-large von Willebrand factor multimers as they are released; without it those multimers persist, platelets adhere to them spontaneously throughout the microcirculation, and the resulting thrombi both consume platelets and shred the red cells passing through. That is why treatment cannot wait for the confirmatory ADAMTS13 assay. Plasma exchange is started within hours of suspicion because it does two things at once, removing the autoantibody and replacing the missing enzyme, and because untreated mortality approaches 90 per cent against roughly 10 to 20 per cent with prompt exchange. High-dose corticosteroids are added, with caplacizumab and rituximab where available. Platelets are withheld unless bleeding is life-threatening, since transfusing them feeds the same microvascular thrombosis.

Key clinical clues

• Microangiopathic hemolysis: schistocytes, high LDH, low haptoglobin, negative Coombs test
• Severe thrombocytopenia with fluctuating, transient neurological symptoms
• Normal PT, aPTT and fibrinogen argue against DIC
• Only mild renal impairment, which argues against HUS, where renal failure dominates
• ADAMTS13 activity severely reduced (<10%), confirming TTP

The case in full

1

Presenting complaint

Patient history

A 38-year-old woman has three days of easy bruising, gum bleeding and worsening fatigue. Today her husband found her briefly confused about where she was, resolving within minutes. There has been no diarrhea, recent illness or new medication.

2

Physical examination

Physical examination

She is afebrile now but has had low-grade fevers at home. There are scattered petechiae over both lower legs, scleral icterus and mild abdominal tenderness, with no organomegaly. Neurology is normal apart from word-finding difficulty that comes and goes.

Measurements

Parameter	Value	Reference
Heart rate	104 bpmRef 60–100	60–100
Blood pressure	128/78 mmHg	–
Temperature	37.8 °CRef 36.1–37.5	36.1–37.5

3

Complete blood count

Laboratory results

A complete blood count is sent.

Measurements

Parameter	Value	Reference
Hemoglobin	7.9 g/dLRef 12.0–15.5	12.0–15.5
Platelets	14 ×10⁹/LRef 150–400	150–400
Reticulocyte count	6.2 %Ref 0.5–2.5	0.5–2.5
White blood cells	8.4 ×10⁹/LRef 4.5–11.0	4.5–11.0

4

Hemolysis and coagulation studies

Laboratory results

Additional studies are sent to characterize the anemia and rule out a coagulopathy.

Measurements

Parameter	Value	Reference
LDH	890 U/LRef 140–280	140–280
Haptoglobin	<10 mg/dLRef 30–200	30–200
Indirect bilirubin	3.4 mg/dLRef 0.2–0.8	0.2–0.8
Direct antiglobulin test (Coombs)	NegativeRef Negative	Negative
PT / aPTT	NormalRef PT 11–14 s, aPTT 25–35 s	PT 11–14 s, aPTT 25–35 s
Fibrinogen	NormalRef 200–400 mg/dL	200–400 mg/dL

5

Peripheral blood smear

Laboratory results

A peripheral blood smear is prepared and reviewed.

6

Renal function and ADAMTS13 activity

Clinical course

Creatinine is only mildly raised, out of proportion to the severity of the hemolysis and thrombocytopenia. With a negative Coombs, normal coagulation and only mild renal involvement, urgent ADAMTS13 activity returns under 10% of normal.