An Investigation into Idiopathic Thrombocytopenic Purpura (ITP)
Elizabeth Wash, Salisbury University
Abstract: Idiopathic Thrombocytopenic Purpura (ITP) is a medical mystery. A disease that affects various components of the immune system has vast treatment methods, and varying symptom presentation leaves all medical professionals without answers, and patients a lifetime of suffering. With limited research available, and the research present all focusing on different aspects of this disease, a synthesis of this knowledge is required to give the best chance at survival for patients. ITP attacks the blood platelets in unconventional ways, preventing the clotting of the blood, allowing for internal bleeding and limited immune system results. While the body is undergoing a strenuous attack from the inside, the symptom presentation varies between patient to patient, but significantly between child and adult, as children are subject to intracranial hemorrhaging, a potentially lethal symptom. The forms and treatments of ITP are variable, as the ITP can be persistent and require more extraneous forms of treatment, while some treatment methods can cause the disease to come out of remission. The lifelong effects of this disease are still somewhat unknown, with there being complications in both one’s physical and emotional state. Idiopathic Thrombocytopenic Purpura is a disorder requiring further research and synthesis to give patients and doctors alike the best chance to combat this disease.
Keywords: Idiopathic Thrombocytopenic Purpura; Petechiae; Purpura; IVIG; Hematoma; Platelets; Megakaryocytes; Autoimmune Disorder; Apoptosis; Splenectomy
Acknowledgments
The author wishes to thank Dr. Jennifer Nyland for her support of this research and comments on earlier drafts of this paper and the support of the Salisbury University Biology Department for their support of this project. The author also wishes to thank the Clarke Honors College at Salisbury University, Dr. Andrew Martino, Dr. Les Erickson, Ms. Candace Henry, and all of the editors that proofread previous drafts of this paper. The NRHC organization is also worthy of thanks for providing valuable experiences for undergraduate students.
Introduction
Idiopathic, or Immune, Thrombocytopenic Purpura (ITP), an autoimmune blood disorder, is a mystery. With a disorder affecting various components of the immune system, most attributes of this disorder must be actively observed in patients who are currently afflicted, but with a rare disease, that is not a simple feat. Several aspects of ITP leave physicians confused on the best treatment options to restore the platelet levels within the blood, treatment of the side effects caused by the lowered platelet count, and how to manage the lifelong effects. There have been a variety of studies, but these studies continue to have numerous unanswered questions, proving that more research is needed to know the true pathophysiology of ITP, symptom presentation, forms and treatment, and the lifelong effects that often go unnoticed.
Pathophysiology of ITP
The destruction caused by ITP on one’s body is caused by a reduction in platelet production, or even a specific antibody targeting the platelets within one’s body. The megakaryocytes have several functions within the body, the main one being the production of blood platelets (Cines et al., 2009). With a disorder that targets the survivability and presence of platelets within the body, it can be determined that a key feature of this disease is due to the megakaryocytes having features of apoptosis (Cines et al., 2009). Apoptosis is a distinct form of cell death, and with patients exhibiting ITP, the majority of megakaryocytes do not reach maturity. Most megakaryocytes show alterations that are comparable to being in the stages of apoptosis in ITP patients (Cines et al., 2009). The result of the main cell involved in blood platelet production being induced early in apoptosis in ITP patients is the main contributor to the symptom presentation and the treatment methods used.
Blood platelets are vital in the clotting of blood within the body, which is necessary when one experiences a cut, bruise, or any injury or infliction. When the platelets are experiencing cell death before maturity, this means that they will not be functional when needed, allowing for blood to roam throughout the body, resulting in substantial internal bleeding, and an overall lower blood volume (Zufferey et al., 2017). This internal bleeding if not appropriately clotted can lead to potentially deadly results, and symptoms that can lead to a lowered immune response, and ultimately damage joints, organs, or tissues (McKenzie et al., 2013). If one was to cut themselves when lacking megakaryocytes, this could lead to substantial blood loss and irreversible results. The diagnosis of ITP is rare, as often the presence of megakaryocytes that are characteristically lacking in ITP, can be the same in patients experiencing leukemia (Zufferey et al., 2017). There must be a further analysis of the morphological changes that are present within the disorder and all blood cells when ITP is suspected or diagnosed in a patient.
Symptom Variation
All individuals are susceptible to being diagnosed with ITP; however, the onset display of symptoms can vary. The presentation of symptoms can vary depending on the nature of diagnosis, whether an individual develops the disorder in adulthood or childhood. The age at which one develops the disorder varies with the severity of the disorder. The presentation of ITP in adults mainly demonstrates internal bleeding, causing hematomas (McMillian et al., 2004). The signs of this internal bleeding are seen in petechiae, purpura, skin discoloration, and blood in urine or stool (NHLBI, 2022). Petechiae is classified as pinpoint spots that appear on the skin as a result of bleeding, often presenting as a rash, while purpura are purple covered patches that can appear on the skin or on mucus membranes (NHLBI, 2022). Both of these symptoms can indicate internal bleeding, as they demonstrate pooling of blood beneath the surface of the skin due to the inability for the blood to clot, a further indication of a blood clotting disorder, such as ITP. While these symptoms can be exhibited in adolescent patients, ITP in childhood can present in several other manners and have deadlier symptoms than the presentation in adulthood. The rarity that accompanies the development of ITP, leads physicians and patients alike left to treat symptoms as they appear.
Idiopathic Thrombocytopenic Purpura has varying symptom presentation in children compared to the symptom presentation in adults. One rare side effect of ITP, when diagnosed in childhood, is intracranial hemorrhage. This complication of ITP, while rare, is of extreme concern, as it has a 25% chance of being lethal, and a 25% chance of having permanent nerve damage, with only a 50% chance of survival with a full recovery (Psaila et al., 2009). This symptom which can accompany the diagnosis of ITP can impact the ability of the children to survive and recover. Idiopathic Thrombocytopenic Purpura is commonly seen to present after the presence of an infection in children, especially between the ages of 1 to 10 years old, and there have been several differences noted between younger to older aged children in symptom presentation and ITP occurrence (Kuhne, 2003). Children developing ITP have differing symptom presentations than adults, contributing to the rarity and lack of knowledge known about this disease.
Forms and Treatment of ITP
There are two main forms of Idiopathic Thrombocytopenic Purpura, which can be acute or long-term. The acute version is classified by having occurred for less than six months, and the chronic version occurring longer than six months (Page et al., 2007). The more common version of ITP is the acute version, and this is present mainly in children, whereas the chronic version typically affects adults more frequently. There can also be the development of secondary forms of ITP as the result of a splenectomy, a common treatment of Idiopathic Thrombocytopenic Purpura, especially in adults (Rodeghiero, 2018). The form that is present within a patient determines the appropriate treatment methods and could be used to predict potential side effects caused by the disorder.
Idiopathic Thrombocytopenic Purpura’s treatment varies depending on the age of the patient, severity of the disorder, and previous medical conditions/history. The basic goals of treatment for ITP are to reduce the risk of bleeding and to create a long-term “cure,” which can be cultivated in different ways depending on both the severity and age of the patient. For infants, a common practice is hospitalization with IVIG transfusion, whereas corticosteroids are often given to older children (Kuhne et al., 2003). IVIG transfusions are a treatment method for specific antibody deficiencies, such as platelets, in which antibodies are directly given to the patient intravenously, to restore the integrity of the blood (Kuhne et al., 2003). The treatment of IVIG restores the number of platelets within a patient’s blood, increasing the efficiency of the immune system and effectively reversing the effects of ITP (Kuhne et al., 2003). Corticosteroid treatment is used to block the immune system, allowing for megakaryocytes to reach maturity, without any internal attacks, and to establish the appropriate number of platelets within one’s blood (Kuhne et al., 2003). Another common treatment method, especially for adults, is that of a splenectomy, as it causes the disorder to become milder, and allow for other treatment methods to work better.
The treatment method of a splenectomy has several potential complications that can be just as deadly as ITP itself, with potential post–surgery infections, sepsis, and blood clots (Rodeghiero, 2018). All treatments for ITP come with a higher risk of thrombosis, as this is a major symptom of Idiopathic Thrombocytopenic Purpura, and if the treatment method fails, it can result in these symptoms being heightened. Overall, the treatment option of splenectomy is typically only used if an individual already has chronic ITP. The spleen removes the damaged or apoptotic platelet cells, so the removal of the spleen will allow for the number of platelets to increase (Rodeghiero, 2018). This increase would be due to allowing more platelets to circulate within the body and restore the platelet levels within one’s blood. Even in the circumstances of having a splenectomy, other treatment methods, such as the use of IVIG transfusions or corticosteroids are used in addition to giving the patient the best chance to overcome the disease.
Lifelong Effects of ITP
There is little information about patients whose treatment for ITP fails, or how this disorder, even in remission, can have unexpected lifelong complications. The current treatment methods are used in sequential order, with corticosteroid therapy and IVIG transfusions being given first, and then if a patient does not respond, one must undergo a splenectomy (Rodeghiero, 2018). The initial approach of either corticosteroid therapy or IVIG transfusion only results in creating a stable response in platelet counts in 60 – 70% of patients (McMillan et al., 2004). When one has a splenectomy they are at a higher risk of becoming sick or not recovering from illnesses. Once a patient has ITP, even if it has been in remission for a long period, they have a higher incidence of other autoimmune disorders than other individuals, and can suffer ITP relapses (McMillan et al., 2004). The first treatment for an individual with ITP to increase their platelet counts is just the beginning for most patients, as there will be several lifelong impacts from this disorder.
Idiopathic Thrombocytopenic Purpura has effects on an individual’s entire being, with results that can last a lifetime, depending on relapses and severity of the disorder. Patients who remain in a chronic ITP can potentially lose an average of 20.4 years of their life expectancy (Mathias et al., 2008). Individuals with ITP or having treatment for ITP have prolonged symptoms of anxiety, depression, fear, exhaustion, and fatigue. Idiopathic Thrombocytopenic Purpura especially impacts women and their ability to reproduce, whether it is having severe and prolonged menstrual bleeding or difficulties getting pregnant, and once pregnant, close monitoring and treatment must be provided (Mathias et al., 2008). This disorder can also impact an individual’s social and work life, forcing one to take a less physical job and to avoid social activities to avoid bruising and internal bleeding (Mathias et al., 2008). The lifelong effects of ITP are not just physical but include the social and emotional parts of an individual, and most effects are still unknown.
Conclusion
Idiopathic Thrombocytopenic Purpura is a rare autoimmune blood disorder, often going misdiagnosed and treated inappropriately. The rarity of this disorder contributes to the lack of knowledge surrounding it, leaving patients stranded with untreatable symptoms, and doctors floundering for potential cures. There is still much to be studied about ITP, but the main conclusion that can be synthesized is that this is a disorder that directly affects megakaryocytes, a cell type that makes blood platelets within the body. This can cause a variety of symptoms and symptom presentations depending on the age and severity of the patient, leading to a few different treatment options. While the treatment options can be combined, no single treatment method is guaranteed to cure or place the patient in remission, resulting in increased uncertainty, especially as the disorder can relapse once an individual is diagnosed. The lifelong effect of ITP ranges to all aspects of one’s life, not just limiting itself to the physical aspects of one’s health. Idiopathic Thrombocytopenic Purpura still is surrounded by unanswered questions, needing more research to provide a better understanding to all, and better quality of care to all patients suffering.
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