Any pipe system has a risk of failure. They can be punctured, or they may rupture if the pressure inside increases rapidly. A human’s blood vessel system is the most complex pipe network, to the extent that, if all blood vessels in your body are laid end to end, they would circle the globe. Theoretically, if a single puncture occurs without a way to repair it, you will lose your blood and die of hypovolemia, but this never occurs.
Why don’t we bleed to death?
Our blood has a complex method to prevent us from bleeding to death. This is called hemostasis, which means “to stop blood”. This system is related to the ability of the blood vessels to contract following injury, minimizing volume loss. Another key aspect is the presence of platelets and coagulation factors. In small injuries, we only need the blood vessels to contract as well as the platelets to plug the opening. In case of greater wounds, following the platelets, other blood proteins called coagulation factors enter a cascade of activation ending in the formation of a tough protein called fibrin, which forms the “blood clot”.
If you thought the word “blood clot” is a bad thing, that’s probably because you pictured someone going into a heart attack or a stroke because of a blood clot, but there’s another side of the coin, which leads us to understand how complex hemostasis is. Against hemostasis, there is another strong system called the fibrinolytic system, which makes sure that no blood clot is formed unless necessary in order to avoid depriving organs from the vital blood supply.
What are platelets?
Platelets are not cells but rather fractions of cells called megakaryocytes, which are found in the bone marrow. Their main function is to stop blood from escaping the blood vessels by plugging any hole that forms in them. If an injury occurs upon contact between platelets and a non-smooth surface, they stick to that surface and begin sending out signals to other platelets to aggregate and plug the defect. This process occurs on a daily basis, because even small bumps or falls can cause blood vessels to rupture, and sometimes with no cause at all.
The normal platelet count is 150,000-450,000 per cubic milliliter. There are many conditions affecting platelet number and functions. In some, there is an increased number, called thrombocytosis, or decreased numbers known as thrombocytopenia. In other conditions, there is a normal platelet count, but they have an impaired function called thrombasthenia or “weak platelets”. The overall picture of such conditions reflects on controlling bleeding in case of decreased numbers and function or unnecessary clot formation in cases of thrombocytosis.
What is immune thrombocytopenic purpura and how does it occur?
Immune thrombocytopenic purpura is a condition consisting of a decreased platelet count. Regarding the name, it has changed several times in the past few decades. In the past, it was known as idiopathic thrombocytopenic purpura. But the term idiopathic was abandoned because it literally means “of an unknown cause”, and the cause is now known to be immune-related. The term purpura is after the famous appearance of small spots of hemorrhage just under the skin. This term is still being used despite the fact that as much as 30% of cases do not have this symptom.
How immune thrombocytopenic purpura develops is quite complex and the real cause behind its immune destruction remains largely unknown. In children, acute immune thrombocytopenic purpura is known to develop following some viral illnesses, some of them as mild as influenza. This is followed by the production of antibodies that target the membrane of platelets. Antibodies serve to slow down platelets and flag them for destruction by large cells called macrophages that are found mainly in the spleen. The net result is a fall in the number of platelets with an inability of the bone marrow to compensate for such an increased destruction.
However, immune thrombocytopenic purpura doesn’t only occur in children and can also affect adults. The type that affects adults is the chronic type, which lasts for more than one year and is more difficult to treat. It is more common in women 30-40 years old and children.
Can thrombocytopenic purpura kill me?
Bleeding is an everyday occurrence, and not being able to stop it can prove to be fatal. The main cause of death in ITP is intracranial hemorrhage, which is bleeding inside your skull cap. The skull in a nearly closed cavity with rigid bones to provide protection for the brain and the blood vessels that supply it with oxygen. Its main strength, however, remains its most vulnerable point. If bleeding occurs in such a closed cavity, pressure increases rapidly and pushes the brain out of small holes in the skull, causing herniation of the brain over the brainstem, which is responsible for breathing. So basically, you die out of suffocation.
The good point in this complication is that it can be expected and prevented. Any patient with a platelet count of 10,000 per cubic milliliter is at a high risk of bleeding and should be treated emergently.
Symptoms of ITP
- In children, symptoms usually occur a few weeks after a viral infection, while in adults, a bleeding disorder especially in adult females is more commonly associated with autoimmune diseases.
- Common symptoms include:
- Spontaneous bleeding from the gums, vagina or lips.
- Bluish patches of bruising or small dotted reddish pimples all over the skin and lips.
- In case of bleeding into the cranial cavity, disturbance of consciousness and headache are the main symptoms.
Diagnosis of ITP
They key of diagnosing ITP is to exclude all other causes of bleeding disorders. Your physician will order a full workup consisting of a complete blood count to make sure that only platelet number is affected. If the count of red blood cells or white blood cells are also affected, it can’t be immune thrombocytopenic purpura and another cause is sought. It may also be necessary to perform a clotting test to make sure that the coagulation system is intact. It is done by a simple slice in the ear lobe or the forearm and if it turns out that the coagulation system is also impaired, the diagnosis of ITP becomes either wrong or incomplete.
Your doctor may also screen for viral infections that may have triggered the condition once the diagnosis is established. Although it can result from minor viral diseases, the possibility of more severe viruses such as hepatitis C or HIV remains.
Other diseases that may present with the same complaint include:
- Drug-induced bleeding: History taking is essential in the medical practice and an overdose or even a normal dose of an antiplatelet drug such as aspirin or an anticoagulant drug as warfarin can cause the same problem.
- Liver disease: Liver diseases can affect both platelets and coagulation since most coagulation factors are manufactured by the liver, and platelets need a protein called thrombopoietin which is chiefly produced in the liver.
- Bone marrow disorders: The bone marrow is the main manufacturing plant for platelets and conditions affecting it will surely cause a fall in platelet numbers. Examples include bone marrow fibrosis and aplastic anemia.
- Cancers: The effect of cancer on the bone marrow is very complex, but some cancers, as in leukemias, exert a direct effect through the invasion of the bone marrow by immature cells that encroach on the mother cells of platelets. Also, tumors release many inflammatory mediators negatively affecting platelet formation in what we call a “tumor microenvironment”.
- Disseminated intravascular coagulation: It is a combined platelet and coagulation factor disorder. It occurs because the body was exposed to an inflammatory or excitatory cause that led to the formation of several clots, consuming both platelets and coagulation factors and causing deficiencies. It is seen in some cases of abortions, severe infections especially in the newborn, and severe bleeding as in road traffic accidents.
How is ITP treated
The treatment of ITP is mainly supportive, aiming towards keeping platelet count high enough to stop severe complications as intracranial bleeding. There is no cure for ITP, and we can only wait for spontaneous resolution of the autoimmune condition, which occurs in most cases.
The treatment regimens differ between children and adults. Since children mostly develop ITP after a viral infection and it is acute. They mostly need no treatment at all beside a careful follow-up. However, if their platelet count falls below the dangerous threshold 10,000-20,000 per cubic milliliter, they receive corticosteroids or anti-Rh therapy. Adults on the other hand have a higher risk of no spontaneous resolution and are therefore started on steroids, IVIG or anti-Rh once they are diagnosed.
Corticosteroids
Corticosteroids are one of the most effective immunosuppressive and anti-inflammatory drugs created, and since the condition is related to a dysregulated immune system, it makes since to tune it down to allow the platelet number to rise. However, corticosteroid still have a wide range of side effects either from their immunosuppressive effect, which leaves the body susceptible to infections to side effects related to adrenal gland suppression causing a severe withdrawal effect if drug withdrawal is done inappropriately. Therefore, best results are when the drug is done for the shortest period possible.
IVIG
IVIG stands for intravenous immunoglobulin. They are antibodies, but they are unique in that they stop the process of platelet destruction. After the antibody that attaches to the platelets, IVIG stop that antibody from destroying the platelet by attaching to it and preventing it from leading the platelet to be destroyed in the spleen. They are used for a multitude of diseases and are considered second-line after corticosteroids.
Anti-Rh
We all know that blood groups are given names like A+ or O-. The names are derived from proteins found on the surface of our red blood cells called antigens. For example, an A+ individual has an A antigen as well as an Rh (+) antigen. They also have antibodies against the B antigens, and this is the basis of blood transfusion matching. In case of Rh-positive individuals, we can inject them to hold on to red blood cells and destroy them using the same system used to destroy platelets. In other words, we sacrifice red blood cells to save the platelets. It may seem strange, but the number of red blood cells and their size are far greater than those of platelets, which turns the effect upon red blood cells minimal.
In adults who had ITP for more than three months, different therapeutic regimens are considered including chemotherapy like rituximab which acts as an immunosuppressive or more recent drugs called TPO-RA. TPO-RA is short for thrombopoietin receptor agonists. These drugs act as the hormone thrombopoietin in stimulating the bone marrow to produce more platelets. The current members of this class are romiplastin and eltrombopag.
Splenectomy
Splenectomy is the surgical removal of the spleen. It can be resorted to in some cases of ITP if other therapies prove ineffective, especially in adults. The idea is that the spleen is the main site of platelet destruction after being coated with autoantibodies, and its removal will decrease their destruction. In fact, it is one of the most effective therapies and platelet count increases rapidly following such therapy. Splenectomy, however, has some drawbacks, including a decreased immunity towards certain bacteria. Therefore, it is left as a last resort and several precautions are done before and after its removal, including the use of vaccines against such organisms and antibiotics.