Case 115 summary

Our patient presented with MAHA, thrombocytopenia and neurological symptoms which prompted further investigations and confirmation of TTP.

Teamhaem have covered TTP previously in case 7, with a different clinical scenario. Therefore the majority of this summary is taken from the previous case. However key areas to this case are pregnancy, refractory diseaseand new advances in treatment.

Acquired TTP is a potentially life threatening thrombotic microangiopathy, caused by a severe deficiency in ADAMTS13 due to the presence of inhibitory autoantibodies. In our case we demonstrated low levels or ADAMTS13 in the presence of antibodies. This results in aggregation of platelets to ultra large vonwillebrand factor multimers causing micro vascular thrombosis which results in organ ischaemia.

Differential

  • Haemolytic uraemic syndrome
  • Malignant hypertension
  • HELLP (haemolysis elevated liver enzymes low platelets)
  • Pre-eclampsia
  • Disseminated intravascular coagulation
  • Autoimmune diseases e.g. anti-phospholipid syndrome, SLE

TTP – clinical syndrome

The classic clinical presentation is often insidious in inset and consists of the pentad:

  • Pyrexia
  • MAHA
  • Fluctuating neurological impairment – may include personality change and drowsiness to seizures and coma
  • Renal failure
  • Thrombocytopenia

TTP – Investigations

The below are to help in the diagnosis of other MAHA and also to point towards a potential cause.

  • Biochemistry: U&E/LFT/Ca/indirect bili/LDH/troponin/amylase
  • Haematology: FBC, film, reticulocyte count/coag/DAT
  • Viral: HIV/Hep B/C
  • Immunology: Autoimmune screen/haptoglobin
  • ADAMTS13 assay
  • Urinalysis
  • ECG
  • CXR
  • TFTs
  • CT head
  • CT chest abdo pelvis, pregnancy test and stool sample if indicated

Management

Taken from BsH guidelines 2014

New therapies

Caplacuzimab may be used in acquired TTP. An anti-vonwillebrand factor nanobody, inhibits the interaction be ultra large Von willebrand factor multimers and platelets. This results in reduce aggregation, producing faster recovery of the platelet count and reduced incidence of thrombosis, and shortening of the acute episode of TTP.

HERCULES trial – Caplacuzimab treatment for acquired thrombotic thrombocytopenic purpura. NEJM January 2019 Scully, M et al

https://t.co/KNjhbSumYo Link to podcast discussing the role of caplacizumab

TTP and pregnancy

Pregnancy can be the initiating event for TTP. This may be acquired or late onset congenital TTP. Patients may present at any point during pregnancy, but the majority of presentation occur at 30+ weeks gestation a or in the immediate post-part in period.

Diagnosis of TTP can be challenging especially in pregnancy. PEX should be started immediately if there is uncertainty in the diagnosis.

Treatment

  • Delivery is the definitive treatment in pregnancy, however it may not guarantee remission.
  • Congenital TTP may be managed with plasma infusions alone.
  • Steroids and PEX comprises main treatment plan
  • PEX can be continued throughout pregnancy and may allow continuation of pregnancy and delivery of a live foetus
  • Rituximab has been used in pregnancy in other conditions (autoimmune/lymphoma) but there is no data available for its use in pregnancy in acute TTP, although it would be considered in a case such as ours.

The following can be considered when managing a pregnancy in a patient with previous TTP

  • Low dose aspirin
  • LMWH
  • Azathioprine
  • Rituximab can be given pre-conceptually to reduce the risk of relapse during pregnancy
  • PEX

Baseline ADAMTS13 level and IgG should be taken and monitored regularly during pregnancy. Treatment plan will depend upon baseline ADAMTS13 levels and often patients will required additional treatments by the third trimester. The obstetric team would require early and regular reviews to perform foetal ultrasound +\- uterine artery doppler. Delivery should be planned for 37weeks gestation.

Pregnancy outcomes are closely related to gestation with pregnancy loss typically occurring in the second trimester.

ADAMTS13 levels may be reduced in other TMAs related to pregnancy I.e HELLP and pre-eclampsia, but ranging from 12% to 40%, and antibodies to ADAMTS13 are not found.

References

HERCULES trial – Caplacuzimab treatment for acquired thrombotic thrombocytopenic purpura. NEJM January 2019 Scully, M et al

Diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. BSH guideline 2014

Thrombotic thrombocytopenic purpura and pregnancy: presentation, management and subsequent pregnancy outcomes. Blood 2014 Scully et al.

TTP diagnosis and management in pregnancy. Thrombosis UK. Prof Marie Scully. https://m.youtube.com/watch?v=-c8BFywDGbs

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