Dr Robert Bird, member of our Medical Advisory Board, has shared information about ITP patients being at an increased risk of blood clots and not just bleeding.

By Dr Robert Bird

The main worry for most people with ITP, and for doctors treating ITP, is bleeding.  Therefore, it may come as a surprise that ITP is also associated with an increased risk of blood clotting, particularly deep vein thrombosis (DVT). Data from the UK ITP registry indicates that people with ITP have a risk ratio of 1.2 (20% increased risk) for developing clots compared to people of similar age without ITP. Another surprise is that blood clots can occur at any platelet count and a low platelet count is not protective.

The increased risk of blood clots is due to the antibodies, which cause ITP “activating” platelets  (making them more sticky).

Safe platelet count for treatment of clots

The treatment of more serious clots involves “blood thinning” medication or anticoagulation. This can be challenging when the platelet count is very low, but it is generally regarded as safe if the platelet count is over 50. Platelets in ITP usually work very well, compared to platelets in patients with other causes of thrombocytopenia, such as chemotherapy or myelodysplasia. For this reason, particularly in the setting of an acute (very recent) thrombosis, most ITP specialists are happy to use anticoagulation with a platelet count greater than 30.

DVT in the leg

Most blood clots occur in the legs, with pain, redness and swelling of the leg being the symptoms of leg DVT. People with a clot in the leg often feel as if they had torn a calf muscle but can’t remember a specific injury.

Splenectomy

Splenectomy is less commonly used in the treatment of ITP with improved access to effective medical therapies. However, in specific situations, it may still be the best treatment for chronic ITP. One of the immediate complications of splenectomy is clotting in the veins close to the spleen. Following splenectomy, up to 5% people may develop symptoms of such a clot (abdominal pain, swelling), but if routine scanning is performed following the operation, clots are reported in more than 50% cases. This may lead to long-term complications. Much like a congested major road,  where traffic will seek alternative routes to complete the journey, a blocked vessel results in “collaterals”, which are expanded alternative channels to ultimately take blood back to the heart. This can result in dilated/enlarged veins called varices in the gut, which can be at risk of bleeding. Long-term, following splenectomy, there is an increased risk of clots in more typical sites, like the leg.

Thrombopoietin receptor agonists (TPORAs)

TPORAs have greatly improved the treatment of chronic ITP. Romiplostim, eltrombopag and avatrombopag are the TPORAs currently available in Australia, although only eltrombopag is available in New Zealand (link to information on TPORAs). It is known that these drugs don’t activate platelets. In trials performed during the development of the TPORAs, there was concern that high platelet counts might increase the risk of clots, and for that reason, trials were designed to suspend treatment when the platelet count was even in the higher part of the normal range. However, when trials were completed and analysis of clots and platelet counts was undertaken, it was found that clots (which were uncommon) could occur at any platelet coun,t and higher platelet counts didn’t increase clotting risk.

Some ITP treatments, such as rituximab and steroids (immunosuppressive drugs), reduce the production of the antibodies that contribute to low platelet counts. These treatments appear to reduce the risk of clots, probably by decreasing the antibody that causes platelet activation. More clots are seen in people with ITP  on TPORAs than on immunosuppression, and it is probable that this increased risk is because TPORAs don’t work by reducing the production of these antibodies.

TPORAs are certainly a reasonable option to increase the platelet count in ITP patients requiring anticoagulation (see below).

Preventing clots

In order to minimise the risk of blood clots for people with ITP, it is important that everyone with a safe and stable platelet count who has risk factors is treated in the same way as those without ITP. This would include the use of drugs such as aspirin or clopidogrel (antiplatelet drugs) for those with previous heart attacks or strokes, blood thinners such as Warfarin, Rivaroxaban, Apixaban or Dabigatran for those with atrial fibrillation (AF). Routine blood thinning injections or tablets should also be used in people with ITP undergoing surgery, provided the platelet count is at a safe level (see above).

There are also things that people with ITP can do to reduce risks. People with a safe platelet count should discuss whether blood-thinning injections or tablets should be used if a long-haul flight is planned. During the flight, it is best to stay hydrated, by drinking plenty of water, doing leg exercises (as shown in the airline in flight magazine) or walking around the cabin and possibly wearing properly fitted compression stockings.