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Velcro

Zheng (2011)

A 45-year-old woman came to the emergency room because she had been suffering from spontaneous bruising on her legs for about two weeks. In addition, she noticed several red spots on her skin. Her menstruation is also noticeably more intense than usual. For several days now, she has additionally been experiencing strong headaches and feels disoriented in the process.

In the ED, blood is drawn for hematology, coagulation and general chemistry.

Parameter

Ref.

Units

Hemoglobin

6.1

7.2-9.5

mmol/L

Thrombocytes

150-400

⋅10⁹/L

Leukocytes

8.6

4-10

⋅10⁹/L

Creatinine

50-95

µmol/L

LDH

606

<248

U/L

CRP

mg/L

Haptoglobin

<0.1

0.4-2.1

g/L

9-12

sec

PTT

24-33

sec

Fibrinogen

2-4

g/L

DAT

NEG

Her lab shows anemia, thrombopenia and elevated LDH. The haptoglobin is immeasurably low. The direct antiglobulin test is negative. This combination of anemia, elevated LDH an unmeasurable haptoglobin and a negative DAT are strong indications of a non immune-mediated intravascular hemolysis. The patient's secondary hemostasis appears to be in order, with normal fibrinogen, prothrombin and activated prothrombin time.

Her blood smear looks as follows;

Schistocytes in peripheral blood. Schistocytes are fragmented erythrocytes resulting from mechanical stress. Also noticeable is the scarcity of thrombocytes. In the last image, a number of schistocytes have been collected for display.

The presence of non-immune mediated hemolysis, a low platelet count as well as the presence of schistocytes raises the suspicion of thrombotic thrombocytopenic purpura (TTP) and plasmapheresis and immunosuppressants are started immediately.

Thrombotic thrombocytopenic purpura is a microangiopathic hemolytic anemia caused by the presence of large von-Willebrand factor multimers in the circulation. These multimers bind platelets, causing thrombosis and a thrombopenia. The thrombopenia then causes an increased risk of bleeding. Erythrocytes break down on aggregates in the circulation, causing anemia, increased LDH and schistocytes. The platelet aggregates can become trapped in the small vessels of the brain and kidneys. In this case, the patient suffered neurological symptoms as a result, something relatively common in TTP.

To confirm the diagnosis, the activity of ADAMTS13 is measured, which is found to be <1%. Antibodies against ADAMTS13 are also detected. As was done in this patient, plasmapheresis should be started immediately if TTP is suspected. This procedure, in which the patient's plasma is replaced with donor plasma, has the function of capturing the ADAMTS13 antibodies and replenishing functional ADAMTS13. Treatment with immunosuppressants aims to prevent the formation of new antibodies.

The presence of vWF multimers can occur when the activity of ADAMTS13 is inhibited, such as by acquired antibodies as in this patient. Normally, ADAMTS13 continuously cuts up vWF multimers into smaller pieces making them less thrombogenic. The exact cause for the generation of these antibodies is unknown.

Plasmapheresis

The patient receives plasmapheresis for 11 days, during which 148 units of plasma are exchanged with the patient's blood. In addition, the patient will receive rituximab and caplacizumab. Rituximab, an anti-CD20 antibody, captures away B cells and serves to prevent new antibody formation. Caplacizumab is an antibody that hinders the binding between platelets and vWF.

Decrease in LDH due to plasmapheresis

Increase in platelet count due to plasmapheresis

This treatment results in a nice drop in LDH and an increase in the platelet count. Finally, a complete haematological remission is seen, which is defined in the guidelines as a platelet count >150*10^9/L and a normal LDH on two consecutive days (after discontinuation of plasmapheresis).

The patient is discharged shortly afterwards and returns several times to check her platelet count.