Impaired blood clotting in haemophiliacs

Since 1997 it has been noted that haemophiliacs receiving Factor VIII for clotting disorders have been experiencing unusual rates of bleeding whilst receiving protease inhibitor treatment. It has been suggested that protease inhibitors could interfere with blood clotting by inhibiting a human enzyme, the serine protease, necessary for proper blood clotting. However, a study has shown that PIs can only be associated with a slowdown in clotting times at very high concentrations, far above those commonly seen in clinical studies. 1

Haemophiliacs may experience specific protease-related side-effects, although it is not known if they are related to the other metabolic changes discussed here. A 1998 study reported that 10 of 17 haemophiliacs on PIs experienced more bleeding and changes in bleeding patterns, compared to the six months prior to protease therapy. 2

A more recent study has suggested that protease inhibitors may have the reverse effect on blood clotting, slowing the clearance of clots and increasing coagulability.3 Further research is needed to confirm these findings.

References

  1. Ermolieff J et al. Inhibition of coagulation factors by HIV protease inhibitors. International Conference on the Discovery and Clinical Development of Antiretroviral Therapies, Virgin Islands, abstract 38, 1998
  2. Stanworth SJ et al. Increased bleeding in HIV-positive haemophiliacs treated with antiretroviral protease inhibitors. Haemophilia 4: 109-114, 1998
  3. Koppel K et al. Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes 29(5): 441-449, 2002
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