Thrombophilia

Thrombophilia is a predisposition to the formation of thrombosis. Its cause may be inherited or acquired.

1) Inherited causes of thrombophilia include:

• Protein C deficiency
• Protein S deficiency
• Antithrombin deficiency
• Activated protein C resistance
• Factor V Leiden (see below)
• Homocysteinuria

2) Acquired causes of thrombophilia include:

• cancer
• pregnancy
• eostrogen therapy
• sickle cell disease
• thrombotic thrombocytopenic purpura (see below)
• nephrotic syndrome
• antiphospholipid antibodies

Factor V Leiden

A point mutation on the gene for clotting factor V results in a variant known as 'factor V Leiden'.
The result of this mutation is that factor V is insensitive to protein C inactivation, resulting in hypercoagulabilty and hence increased risk of PEs/DVTs and even Budd Chiari syndrome.

Factor V Leiden is inherited in an autosomal dominant fashion with incomplete penetrance.



Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura is a condition in which systemic thrombi develop formed of platelets and Von Willebrand factor
The 5 key features are:

• Thrombocytopenic purpura
• Microangiopathic haemolytic anaemia
• Renal failure
• Fever
• Fluctuating neurological dysfunction

Thrombotic thrombocytopenic purpura may be either:

• Congenital = mutation of ADAMTS13 allelle (AKA Upshaw-Schulman syndrome)
• Acquired = autoantibodies against ADAMTS13

Adult females are most commonly affected

Treatment is:

• Plasma exchange
• Second line therapies include: vincristine, splenectomy, cyclosporine, azothioprine
• Possibly rituximab

Without treatment mortality is around 90%; with treatment mortality decreases to 10%.

References:
Bertina, R. Factor V Leien and other coagulation factor mutations affecting thrombotic risk. Clin Chem. 1997; 43(9): 1678-1683.
Galbusera, M., Noris, M. and Remuzzi, G. Inherited thrombotic thrombocytopenic purpura. Haemtologica. 2009; 94(2): 166-170.
Han-Mou, T. Current concepts in thrombotic thrombocytopenic purpura. Annu Rev Med. 2006; 57: 419-436.
Han-Mou, T. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hamatol. 2010; 91(1): 1-19.
Helt, J. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007: 127-135.