Thrombosis

General paediatrics, Haem/Oncology

The basic coagulation screen is PT, APTT and Fibrinogen.

  • PT – liver disease, warfarin, DIC
  • APTT – haemophilia, heparin, DIC, anticoagulant eg lupus anticoagulant
  • Fibrinogen – congenital hypofibrinogenaemia, DIC

A prolonged APTT which corrects (at least partially) on mixing with normal plasma is deficient in clotting factors. If correction is not possible, then must be an anticoagulant.

The more advanced coagulation tests are:

  • Diluted Russel Viper Venom Time (DRVVT)
  • Kaolin Clotting Time (KCT)

Basic thrombophilia screen is:

  • Protein C/S
  • Anti-thrombin III
  • Prothrombin mutations
  • Factor V Leiden mutation
  • Homocysteine

Protein C and S can be transiently low with acute thrombosis. Levels also affected by warfarin but not by LMWH.

Factor V Leiden

Most common inherited thromophilia in Europe. Co factor for factor X. Autosomal dominant so variable penetrance. Rare in East Asian and African.

Anti-Phospholipid Syndrome

Antiphospholipid antibodies are a mixed bag:

  • Lupus anticoagulant – total misnomer, as it is PRO-thrombotic and only occasionally associated with lupus! Anticoagulant only in vitro. Overall, found in 1-5% of normal population, though in low titre, usually IgM and transient. Persistent positivity is strongly associated with venous thrombosis and stroke and fetal loss.
  • Anticardiolipin is more associated with pregnancy morbidity than with thrombosis, and is less predictive than LA.
  • Anti beta2 glycoprotein 1 (beta2Gp1) antibodies are less well established as an independent risk factor but are cumulative with the other 2.

An autoimmune disorder of recurrent thrombosis and pregnancy loss! Migraine, livedo, raynauds, unexplained persistent thrombocytopenia can be clues. Not well defined in children, usually heralds SLE and is probably much the same thing.

There is no one antiphospholipid syndrome, despite the name! All have persistent antiphospholipid antibodies (of one sort or another) plus 1 or more clinical criteria:

  1. thrombosis
  2. pregnancy related morbidity:
    • unexplained IUD beyond 10/40 with normal morphology
    • preterm (<34/40) due to pre-eclampsia/placental insuff
    • 3+ unexplained consecutive miscarriages

For lab, must test positive on 2 occasions, 12+/52 apart. Testing is affected by warfarin and heparin.

Antiphospholipid syndrome occurs in isolation in more than 50%. 30% of SLE patients get it. A catastrophic clinical presentation can occur with multiorgan involvement (pulmonary haemorrhage, ARDS, cerebral/adrenal infarction, Budd-Chiari), microangiopathic thrombocytopenia, haemolysis similar to TTP/HUS/DIC (Rx anticoagulation, high dose steroids, plasma exchange, IVIG).

Acute treatment is with IV or subcut heparin, followed by warfarin (target INR 2-3). Aspirin may be added if problematic. Hydroxychloroquine should probably always be used. Avoid smoking, oestrogens, cocaine… Plasma exchange and Rituximab may be used in life-threatening cases.

The antibodies act by inducing adhesion molecules from endothelial cells, upregulating tissue factor, activating platelets and the complement cascade generally.  [Current Opinion in Hematology. 13(5):366-75, 2006]

[BMJ 2010:340;1125]